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Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Review

Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review

Authors: Jiang Jiang, Hailong Li, Eskandar Qaed, Jing Zhang, Yushu Song, Rong Wu, Xinmiao Bu, Qinyan Wang, Zeyao Tang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Since Salinomycin (Sal) emerged its ability to target breast cancer stem cells in 2009, numerous experiments have been carried out to test Sal’s anticancer effects. What deserve to be mentioned is that Sal can efficiently induce proliferation inhibition, cell death and metastasis suppression against human cancers from different origins both in vivo and in vitro without causing serious side effects as the conventional chemotherapeutical drugs on the body. There may be novel cell death pathways involving the anticancer effects of Sal except the conventional pathways, such as autophagic pathway. This review is focused on how autophagy involves the effects of Sal, trying to describe clearly and systematically why autophagy plays a vital role in predominant anticancer effects of Sal, including its distinctive characteristic. Based on recent advances, we present evidence that a dual role of Sal involving in autophagy may account for its unique anticancer effects - the preference for cancer cells. Further researches are required to confirm the authenticity of this suppose in order to develop an ideal anticancer drug.
Literature
2.
go back to reference Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (London, England). 2012;7(4):597–615.CrossRef Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (London, England). 2012;7(4):597–615.CrossRef
3.
go back to reference Shibata M, Shen MM. The roots of cancer: stem cells and the basis for tumor heterogeneity. BioEssays : news and reviews in molecular, cellular and developmental biology. 2013;35(3):253–60.CrossRef Shibata M, Shen MM. The roots of cancer: stem cells and the basis for tumor heterogeneity. BioEssays : news and reviews in molecular, cellular and developmental biology. 2013;35(3):253–60.CrossRef
4.
go back to reference Chen D, Wu M, Li Y, Chang I, Yuan Q, Ekimyan-Salvo M, Deng P, Yu B, Yu Y, Dong J, et al. Targeting BMI1+ cancer stem cells overcomes Chemoresistance and inhibits metastases in squamous cell carcinoma. Cell Stem Cell. 2017;20(5):621–634.e626.PubMedCrossRef Chen D, Wu M, Li Y, Chang I, Yuan Q, Ekimyan-Salvo M, Deng P, Yu B, Yu Y, Dong J, et al. Targeting BMI1+ cancer stem cells overcomes Chemoresistance and inhibits metastases in squamous cell carcinoma. Cell Stem Cell. 2017;20(5):621–634.e626.PubMedCrossRef
5.
go back to reference Miyazaki Y, Shibuya M, Sugawara H, Kawaguchi O, Hirsoe C. Salinomycin, a new polyether antibiotic. The Journal of antibiotics. 1974;27(11):814–21.PubMedCrossRef Miyazaki Y, Shibuya M, Sugawara H, Kawaguchi O, Hirsoe C. Salinomycin, a new polyether antibiotic. The Journal of antibiotics. 1974;27(11):814–21.PubMedCrossRef
6.
go back to reference Schafer H, Clauss W, Hornicke H. Cationophore properties of the new polyether antibiotic Salinomycin investigated in distal rabbit colon in vivo and in vitro. Comparative biochemistry and physiology A, Comparative Physiology. 1984;79(3):387–92.PubMedCrossRef Schafer H, Clauss W, Hornicke H. Cationophore properties of the new polyether antibiotic Salinomycin investigated in distal rabbit colon in vivo and in vitro. Comparative biochemistry and physiology A, Comparative Physiology. 1984;79(3):387–92.PubMedCrossRef
7.
go back to reference Naujokat C, Fuchs D, Opelz G. Salinomycin in cancer: a new mission for an old agent. Mol Med Rep. 2010;3(4):555–9.PubMedCrossRef Naujokat C, Fuchs D, Opelz G. Salinomycin in cancer: a new mission for an old agent. Mol Med Rep. 2010;3(4):555–9.PubMedCrossRef
8.
go back to reference Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138(4):645–59.PubMedPubMedCentralCrossRef Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138(4):645–59.PubMedPubMedCentralCrossRef
9.
go back to reference Antoszczak M, Huczynski A. Anticancer activity of polyether Ionophore-Salinomycin. Anti Cancer Agents Med Chem. 2015;15(5):575–91.CrossRef Antoszczak M, Huczynski A. Anticancer activity of polyether Ionophore-Salinomycin. Anti Cancer Agents Med Chem. 2015;15(5):575–91.CrossRef
10.
go back to reference Calzolari A, Saulle E, De Angelis ML, Pasquini L, Boe A, Pelacchi F, Ricci-Vitiani L, Baiocchi M, Testa U. Salinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell lines. PLoS One. 2014;9(4):e94438.PubMedPubMedCentralCrossRef Calzolari A, Saulle E, De Angelis ML, Pasquini L, Boe A, Pelacchi F, Ricci-Vitiani L, Baiocchi M, Testa U. Salinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell lines. PLoS One. 2014;9(4):e94438.PubMedPubMedCentralCrossRef
11.
go back to reference He L, Wang F, Dai WQ, Wu D, Lin CL, Wu SM, Cheng P, Zhang Y, Shen M, Wang CF, et al. Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines. Pancreatology : official journal of the International Association of Pancreatology (IAP) [et al]. 2013;13(1):72–8.CrossRef He L, Wang F, Dai WQ, Wu D, Lin CL, Wu SM, Cheng P, Zhang Y, Shen M, Wang CF, et al. Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines. Pancreatology : official journal of the International Association of Pancreatology (IAP) [et al]. 2013;13(1):72–8.CrossRef
12.
go back to reference Larzabal L, El-Nikhely N, Redrado M, Seeger W, Savai R, Calvo A. Differential effects of drugs targeting cancer stem cell (CSC) and non-CSC populations on lung primary tumors and metastasis. PLoS One. 2013;8(11):e79798.PubMedPubMedCentralCrossRef Larzabal L, El-Nikhely N, Redrado M, Seeger W, Savai R, Calvo A. Differential effects of drugs targeting cancer stem cell (CSC) and non-CSC populations on lung primary tumors and metastasis. PLoS One. 2013;8(11):e79798.PubMedPubMedCentralCrossRef
13.
go back to reference Daman Z, Montazeri H, Azizi M, Rezaie F, Ostad SN, Amini M, Gilani K. Polymeric micelles of PEG-PLA copolymer as a carrier for Salinomycin against gemcitabine-resistant pancreatic cancer. Pharm Res. 2015;32(11):3756–67.PubMedCrossRef Daman Z, Montazeri H, Azizi M, Rezaie F, Ostad SN, Amini M, Gilani K. Polymeric micelles of PEG-PLA copolymer as a carrier for Salinomycin against gemcitabine-resistant pancreatic cancer. Pharm Res. 2015;32(11):3756–67.PubMedCrossRef
14.
go back to reference Parajuli B, Shin SJ, Kwon SH, Cha SD, Chung R, Park WJ, Lee HG, Cho CH. Salinomycin induces apoptosis via death receptor-5 up-regulation in cisplatin-resistant ovarian cancer cells. Anticancer Res. 2013;33(4):1457–62.PubMed Parajuli B, Shin SJ, Kwon SH, Cha SD, Chung R, Park WJ, Lee HG, Cho CH. Salinomycin induces apoptosis via death receptor-5 up-regulation in cisplatin-resistant ovarian cancer cells. Anticancer Res. 2013;33(4):1457–62.PubMed
15.
go back to reference Kim WK, Kim JH, Yoon K, Kim S, Ro J, Kang HS, Yoon S. Salinomycin, a p-glycoprotein inhibitor, sensitizes radiation-treated cancer cells by increasing DNA damage and inducing G2 arrest. Investig New Drugs. 2012;30(4):1311–8.CrossRef Kim WK, Kim JH, Yoon K, Kim S, Ro J, Kang HS, Yoon S. Salinomycin, a p-glycoprotein inhibitor, sensitizes radiation-treated cancer cells by increasing DNA damage and inducing G2 arrest. Investig New Drugs. 2012;30(4):1311–8.CrossRef
16.
go back to reference Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C. Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun. 2009;390(3):743–9.PubMedCrossRef Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C. Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun. 2009;390(3):743–9.PubMedCrossRef
17.
go back to reference Ketola K, Hilvo M, Hyotylainen T, Vuoristo A, Ruskeepaa AL, Oresic M, Kallioniemi O, Iljin K. Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 2012;106(1):99–106.PubMedPubMedCentralCrossRef Ketola K, Hilvo M, Hyotylainen T, Vuoristo A, Ruskeepaa AL, Oresic M, Kallioniemi O, Iljin K. Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 2012;106(1):99–106.PubMedPubMedCentralCrossRef
18.
go back to reference Zhen YF, Li ST, Zhu YR, Wang XD, Zhou XZ, Zhu LQ. Identification of DNA-PKcs as a primary resistance factor of salinomycin in osteosarcoma cells. Oncotarget. 2016;7(48):79417–27.PubMedPubMedCentralCrossRef Zhen YF, Li ST, Zhu YR, Wang XD, Zhou XZ, Zhu LQ. Identification of DNA-PKcs as a primary resistance factor of salinomycin in osteosarcoma cells. Oncotarget. 2016;7(48):79417–27.PubMedPubMedCentralCrossRef
20.
go back to reference Kim SH, Choi YJ, Kim KY, Yu SN, Seo YK, Chun SS, Noh KT, Suh JT, Ahn SC. Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells. Biochem Biophys Res Commun. 2016;473(2):607–13.PubMedCrossRef Kim SH, Choi YJ, Kim KY, Yu SN, Seo YK, Chun SS, Noh KT, Suh JT, Ahn SC. Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells. Biochem Biophys Res Commun. 2016;473(2):607–13.PubMedCrossRef
21.
go back to reference Zhang C, Tian Y, Song F, Fu C, Han B, Wang Y. Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells. Oncol Rep. 2015;34(5):2469–76.PubMedCrossRef Zhang C, Tian Y, Song F, Fu C, Han B, Wang Y. Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells. Oncol Rep. 2015;34(5):2469–76.PubMedCrossRef
22.
go back to reference Zhang Y, Zuo Y, Guan Z, Lu W, Xu Z, Zhang H, Yang Y, Yang M, Zhu H, Chen X. Salinomycin radiosensitizes human nasopharyngeal carcinoma cell line CNE-2 to radiation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37(1):305–11.CrossRef Zhang Y, Zuo Y, Guan Z, Lu W, Xu Z, Zhang H, Yang Y, Yang M, Zhu H, Chen X. Salinomycin radiosensitizes human nasopharyngeal carcinoma cell line CNE-2 to radiation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37(1):305–11.CrossRef
23.
go back to reference Niwa AM, GF DE, Marques LA, Semprebon SC, Sartori D, Ribeiro LR, Mantovani MS. Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells. Naunyn Schmiedeberg's Arch Pharmacol. 2016;389(6):557–71.CrossRef Niwa AM, GF DE, Marques LA, Semprebon SC, Sartori D, Ribeiro LR, Mantovani MS. Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells. Naunyn Schmiedeberg's Arch Pharmacol. 2016;389(6):557–71.CrossRef
24.
go back to reference Hermawan A, Wagner E, Roidl A. Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity. Oncol Rep. 2016;35(3):1732–40.PubMedCrossRef Hermawan A, Wagner E, Roidl A. Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity. Oncol Rep. 2016;35(3):1732–40.PubMedCrossRef
25.
go back to reference Koo KH, Kim H, Bae YK, Kim K, Park BK, Lee CH, Kim YN. Salinomycin induces cell death via inactivation of Stat3 and downregulation of Skp2. Cell Death Dis. 2013;4:e693.PubMedPubMedCentralCrossRef Koo KH, Kim H, Bae YK, Kim K, Park BK, Lee CH, Kim YN. Salinomycin induces cell death via inactivation of Stat3 and downregulation of Skp2. Cell Death Dis. 2013;4:e693.PubMedPubMedCentralCrossRef
26.
go back to reference Sun P, Pavlostathis SG, Huang CH. Photodegradation of veterinary ionophore antibiotics under UV and solar irradiation. Environmental science & technology. 2014;48(22):13188–96.CrossRef Sun P, Pavlostathis SG, Huang CH. Photodegradation of veterinary ionophore antibiotics under UV and solar irradiation. Environmental science & technology. 2014;48(22):13188–96.CrossRef
27.
go back to reference Yao H, Sun P, Minakata D, Crittenden JC, Huang CH. Kinetics and modeling of degradation of ionophore antibiotics by UV and UV/H2O2. Environmental science & technology. 2013;47(9):4581–9.CrossRef Yao H, Sun P, Minakata D, Crittenden JC, Huang CH. Kinetics and modeling of degradation of ionophore antibiotics by UV and UV/H2O2. Environmental science & technology. 2013;47(9):4581–9.CrossRef
28.
go back to reference Riccioni R, Dupuis ML, Bernabei M, Petrucci E, Pasquini L, Mariani G, Cianfriglia M, Testa U. The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis. 2010;45(1):86–92.PubMedCrossRef Riccioni R, Dupuis ML, Bernabei M, Petrucci E, Pasquini L, Mariani G, Cianfriglia M, Testa U. The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis. 2010;45(1):86–92.PubMedCrossRef
29.
go back to reference Zhang ZM, Wu JF, Luo QC, Liu QF, Wu QW, Ye GD, She HQ, Li BA. Pygo2 activates MDR1 expression and mediates chemoresistance in breast cancer via the Wnt/beta-catenin pathway. Oncogene. 2016;35(36):4787–97.PubMedCrossRef Zhang ZM, Wu JF, Luo QC, Liu QF, Wu QW, Ye GD, She HQ, Li BA. Pygo2 activates MDR1 expression and mediates chemoresistance in breast cancer via the Wnt/beta-catenin pathway. Oncogene. 2016;35(36):4787–97.PubMedCrossRef
30.
go back to reference Lu Y, Ma W, Mao J, Yu X, Hou Z, Fan S, Song B, Wang H, Li J, Kang L, et al. Salinomycin exerts anticancer effects on human breast carcinoma MCF-7 cancer stem cells via modulation of hedgehog signaling. Chem Biol Interact. 2015;228:100–7.PubMedCrossRef Lu Y, Ma W, Mao J, Yu X, Hou Z, Fan S, Song B, Wang H, Li J, Kang L, et al. Salinomycin exerts anticancer effects on human breast carcinoma MCF-7 cancer stem cells via modulation of hedgehog signaling. Chem Biol Interact. 2015;228:100–7.PubMedCrossRef
31.
go back to reference He M, Fu Y, Yan Y, Xiao Q, Wu H, Yao W, Zhao H, Zhao L, Jiang Q, Yu Z, et al. The hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells in breast cancer patients. Clinical science (London, England : 1979). 2015;129(9):809–22.CrossRef He M, Fu Y, Yan Y, Xiao Q, Wu H, Yao W, Zhao H, Zhao L, Jiang Q, Yu Z, et al. The hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells in breast cancer patients. Clinical science (London, England : 1979). 2015;129(9):809–22.CrossRef
32.
go back to reference Kim JH, Chae M, Kim WK, Kim YJ, Kang HS, Kim HS, Yoon S. Salinomycin sensitizes cancer cells to the effects of doxorubicin and etoposide treatment by increasing DNA damage and reducing p21 protein. Br J Pharmacol. 2011;162(3):773–84.PubMedPubMedCentralCrossRef Kim JH, Chae M, Kim WK, Kim YJ, Kang HS, Kim HS, Yoon S. Salinomycin sensitizes cancer cells to the effects of doxorubicin and etoposide treatment by increasing DNA damage and reducing p21 protein. Br J Pharmacol. 2011;162(3):773–84.PubMedPubMedCentralCrossRef
33.
go back to reference Srivastava AK, Han C, Zhao R, Cui T, Dai Y, Mao C, Zhao W, Zhang X, Yu J, Wang QE. Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells. Proc Natl Acad Sci U S A. 2015;112(14):4411–6.PubMedPubMedCentralCrossRef Srivastava AK, Han C, Zhao R, Cui T, Dai Y, Mao C, Zhao W, Zhang X, Yu J, Wang QE. Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells. Proc Natl Acad Sci U S A. 2015;112(14):4411–6.PubMedPubMedCentralCrossRef
34.
go back to reference Krause M, Dubrovska A, Linge A, Baumann M. Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv Rev. 2017;109:63–73.PubMedCrossRef Krause M, Dubrovska A, Linge A, Baumann M. Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv Rev. 2017;109:63–73.PubMedCrossRef
36.
go back to reference Rebecca VW, Amaravadi RK. Emerging strategies to effectively target autophagy in cancer. Oncogene. 2016;35(1):1–11.PubMedCrossRef Rebecca VW, Amaravadi RK. Emerging strategies to effectively target autophagy in cancer. Oncogene. 2016;35(1):1–11.PubMedCrossRef
37.
go back to reference Marino G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 2014;15(2):81–94.PubMedPubMedCentralCrossRef Marino G, Niso-Santano M, Baehrecke EH, Kroemer G. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 2014;15(2):81–94.PubMedPubMedCentralCrossRef
40.
go back to reference Verdoodt B, Vogt M, Schmitz I, Liffers ST, Tannapfel A, Mirmohammadsadegh A. Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One. 2012;7(9):e44132.PubMedPubMedCentralCrossRef Verdoodt B, Vogt M, Schmitz I, Liffers ST, Tannapfel A, Mirmohammadsadegh A. Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One. 2012;7(9):e44132.PubMedPubMedCentralCrossRef
41.
go back to reference Mirkheshti N, Park S, Jiang S, Cropper J, Werner SL, Song CS, Chatterjee B. Dual targeting of androgen receptor and mTORC1 by salinomycin in prostate cancer. Oncotarget. 2016;7(38):62240–54.PubMedPubMedCentralCrossRef Mirkheshti N, Park S, Jiang S, Cropper J, Werner SL, Song CS, Chatterjee B. Dual targeting of androgen receptor and mTORC1 by salinomycin in prostate cancer. Oncotarget. 2016;7(38):62240–54.PubMedPubMedCentralCrossRef
42.
go back to reference Zhu LQ, Zhen YF, Zhang Y, Guo ZX, Dai J, Wang XD. Salinomycin activates AMP-activated protein kinase-dependent autophagy in cultured osteoblastoma cells: a negative regulator against cell apoptosis. PLoS One. 2013;8(12):e84175.PubMedPubMedCentralCrossRef Zhu LQ, Zhen YF, Zhang Y, Guo ZX, Dai J, Wang XD. Salinomycin activates AMP-activated protein kinase-dependent autophagy in cultured osteoblastoma cells: a negative regulator against cell apoptosis. PLoS One. 2013;8(12):e84175.PubMedPubMedCentralCrossRef
43.
go back to reference Li T, Su L, Zhong N, Hao X, Zhong D, Singhal S, Liu X. Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells. Autophagy. 2013;9(7):1057–68.PubMedPubMedCentralCrossRef Li T, Su L, Zhong N, Hao X, Zhong D, Singhal S, Liu X. Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells. Autophagy. 2013;9(7):1057–68.PubMedPubMedCentralCrossRef
44.
go back to reference Xie F, Zhang S, Liu J, Gong Z, Yang K, Zhang H, Lu Y, Zou H, Yu Y, Chen Y, et al. Codelivery of salinomycin and chloroquine by liposomes enables synergistic antitumor activity in vitro. Nanomedicine (London, England). 2016;11(14):1831–46.CrossRef Xie F, Zhang S, Liu J, Gong Z, Yang K, Zhang H, Lu Y, Zou H, Yu Y, Chen Y, et al. Codelivery of salinomycin and chloroquine by liposomes enables synergistic antitumor activity in vitro. Nanomedicine (London, England). 2016;11(14):1831–46.CrossRef
45.
go back to reference Yue W, Hamai A, Tonelli G, Bauvy C, Nicolas V, Tharinger H, Codogno P, Mehrpour M. Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance. Autophagy. 2013;9(5):714–29.PubMedPubMedCentralCrossRef Yue W, Hamai A, Tonelli G, Bauvy C, Nicolas V, Tharinger H, Codogno P, Mehrpour M. Inhibition of the autophagic flux by salinomycin in breast cancer stem-like/progenitor cells interferes with their maintenance. Autophagy. 2013;9(5):714–29.PubMedPubMedCentralCrossRef
46.
go back to reference Xipell E, Gonzalez-Huarriz M, Martinez de Irujo JJ, Garcia-Garzon A, Lang FF, Jiang H, Fueyo J, Gomez-Manzano C, Alonso MM. Salinomycin induced ROS results in abortive autophagy and leads to regulated necrosis in glioblastoma. Oncotarget. 2016;7(21):30626–41.PubMedPubMedCentralCrossRef Xipell E, Gonzalez-Huarriz M, Martinez de Irujo JJ, Garcia-Garzon A, Lang FF, Jiang H, Fueyo J, Gomez-Manzano C, Alonso MM. Salinomycin induced ROS results in abortive autophagy and leads to regulated necrosis in glioblastoma. Oncotarget. 2016;7(21):30626–41.PubMedPubMedCentralCrossRef
47.
go back to reference Klose J, Stankov MV, Kleine M, Ramackers W, Panayotova-Dimitrova D, Jager MD, Klempnauer J, Winkler M, Bektas H, Behrens GM, et al. Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells. PLoS One. 2014;9(5):e95970.PubMedPubMedCentralCrossRef Klose J, Stankov MV, Kleine M, Ramackers W, Panayotova-Dimitrova D, Jager MD, Klempnauer J, Winkler M, Bektas H, Behrens GM, et al. Inhibition of autophagic flux by salinomycin results in anti-cancer effect in hepatocellular carcinoma cells. PLoS One. 2014;9(5):e95970.PubMedPubMedCentralCrossRef
48.
go back to reference Hashim AI, Zhang X, Wojtkowiak JW, Martinez GV, Gillies RJ. Imaging pH and metastasis. NMR Biomed. 2011;24(6):582–91.PubMedPubMedCentral Hashim AI, Zhang X, Wojtkowiak JW, Martinez GV, Gillies RJ. Imaging pH and metastasis. NMR Biomed. 2011;24(6):582–91.PubMedPubMedCentral
49.
go back to reference Lindner D, Raghavan D. Intra-tumoural extra-cellular pH: a useful parameter of response to chemotherapy in syngeneic tumour lines. Br J Cancer. 2009;100(8):1287–91.PubMedPubMedCentralCrossRef Lindner D, Raghavan D. Intra-tumoural extra-cellular pH: a useful parameter of response to chemotherapy in syngeneic tumour lines. Br J Cancer. 2009;100(8):1287–91.PubMedPubMedCentralCrossRef
50.
go back to reference Gallagher FA, Kettunen MI, Day SE, Hu DE, Ardenkjaer-Larsen JH, Zandt R, Jensen PR, Karlsson M, Golman K, Lerche MH, et al. Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature. 2008;453(7197):940–3.PubMedCrossRef Gallagher FA, Kettunen MI, Day SE, Hu DE, Ardenkjaer-Larsen JH, Zandt R, Jensen PR, Karlsson M, Golman K, Lerche MH, et al. Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nature. 2008;453(7197):940–3.PubMedCrossRef
51.
go back to reference Robey IF, Baggett BK, Kirkpatrick ND, Roe DJ, Dosescu J, Sloane BF, Hashim AI, Morse DL, Raghunand N, Gatenby RA, et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res. 2009;69(6):2260–8.PubMedPubMedCentralCrossRef Robey IF, Baggett BK, Kirkpatrick ND, Roe DJ, Dosescu J, Sloane BF, Hashim AI, Morse DL, Raghunand N, Gatenby RA, et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res. 2009;69(6):2260–8.PubMedPubMedCentralCrossRef
52.
go back to reference Pellegrini P, Dyczynski M, Sbrana FV, Karlgren M, Buoncervello M, Hagg-Olofsson M, Ma R, Hartman J, Bajalica-Lagercrantz S, Grander D, et al. Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells. Oncotarget. 2016;7(24):35703–23.PubMedPubMedCentralCrossRef Pellegrini P, Dyczynski M, Sbrana FV, Karlgren M, Buoncervello M, Hagg-Olofsson M, Ma R, Hartman J, Bajalica-Lagercrantz S, Grander D, et al. Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells. Oncotarget. 2016;7(24):35703–23.PubMedPubMedCentralCrossRef
53.
go back to reference Lagas JS, Sparidans RW, van Waterschoot RA, Wagenaar E, Beijnen JH, Schinkel AH. P-glycoprotein limits oral availability, brain penetration, and toxicity of an anionic drug, the antibiotic salinomycin. Antimicrob Agents Chemother. 2008;52(3):1034–9.PubMedCrossRef Lagas JS, Sparidans RW, van Waterschoot RA, Wagenaar E, Beijnen JH, Schinkel AH. P-glycoprotein limits oral availability, brain penetration, and toxicity of an anionic drug, the antibiotic salinomycin. Antimicrob Agents Chemother. 2008;52(3):1034–9.PubMedCrossRef
54.
go back to reference Jangamreddy JR, Panigrahi S, Los MJ. Monitoring of autophagy is complicated--salinomycin as an example. Biochim Biophys Acta. 2015;1853(3):604–10.PubMedCrossRef Jangamreddy JR, Panigrahi S, Los MJ. Monitoring of autophagy is complicated--salinomycin as an example. Biochim Biophys Acta. 2015;1853(3):604–10.PubMedCrossRef
55.
go back to reference Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science (New York, NY). 2012;337(6098):1062–5.CrossRef Youle RJ, van der Bliek AM. Mitochondrial fission, fusion, and stress. Science (New York, NY). 2012;337(6098):1062–5.CrossRef
57.
go back to reference Koshiba T, Detmer SA, Kaiser JT, Chen H, JM MC, Chan DC. Structural basis of mitochondrial tethering by mitofusin complexes. Science (New York, NY). 2004;305(5685):858–62.CrossRef Koshiba T, Detmer SA, Kaiser JT, Chen H, JM MC, Chan DC. Structural basis of mitochondrial tethering by mitofusin complexes. Science (New York, NY). 2004;305(5685):858–62.CrossRef
58.
go back to reference Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, Smith CL, Youle RJ. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell. 2001;1(4):515–25.PubMedCrossRef Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, Smith CL, Youle RJ. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell. 2001;1(4):515–25.PubMedCrossRef
59.
go back to reference Taguchi N, Ishihara N, Jofuku A, Oka T, Mihara K. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem. 2007;282(15):11521–9.PubMedCrossRef Taguchi N, Ishihara N, Jofuku A, Oka T, Mihara K. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem. 2007;282(15):11521–9.PubMedCrossRef
60.
go back to reference Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003;160(2):189–200.PubMedPubMedCentralCrossRef Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003;160(2):189–200.PubMedPubMedCentralCrossRef
61.
go back to reference Rehman J, Zhang HJ, Toth PT, Zhang Y, Marsboom G, Hong Z, Salgia R, Husain AN, Wietholt C, Archer SL. Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2012;26(5):2175–86.CrossRef Rehman J, Zhang HJ, Toth PT, Zhang Y, Marsboom G, Hong Z, Salgia R, Husain AN, Wietholt C, Archer SL. Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2012;26(5):2175–86.CrossRef
62.
go back to reference Jangamreddy JR, Ghavami S, Grabarek J, Kratz G, Wiechec E, Fredriksson BA, Rao Pariti RK, Cieslar-Pobuda A, Panigrahi S, Los MJ. Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Biochim Biophys Acta. 2013;1833(9):2057–69.PubMedCrossRef Jangamreddy JR, Ghavami S, Grabarek J, Kratz G, Wiechec E, Fredriksson BA, Rao Pariti RK, Cieslar-Pobuda A, Panigrahi S, Los MJ. Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells. Biochim Biophys Acta. 2013;1833(9):2057–69.PubMedCrossRef
63.
go back to reference Michelakis ED, Sutendra G, Dromparis P, Webster L, Haromy A, Niven E, Maguire C, Gammer TL, Mackey JR, Fulton D, et al. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med. 2010;2(31):31ra34.PubMedCrossRef Michelakis ED, Sutendra G, Dromparis P, Webster L, Haromy A, Niven E, Maguire C, Gammer TL, Mackey JR, Fulton D, et al. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med. 2010;2(31):31ra34.PubMedCrossRef
64.
go back to reference Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007;11(1):37–51.PubMedCrossRef Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007;11(1):37–51.PubMedCrossRef
66.
go back to reference Boehmerle W, Muenzfeld H, Springer A, Huehnchen P, Endres M. Specific targeting of neurotoxic side effects and pharmacological profile of the novel cancer stem cell drug salinomycin in mice. Journal of molecular medicine (Berlin, Germany). 2014;92(8):889–900.CrossRef Boehmerle W, Muenzfeld H, Springer A, Huehnchen P, Endres M. Specific targeting of neurotoxic side effects and pharmacological profile of the novel cancer stem cell drug salinomycin in mice. Journal of molecular medicine (Berlin, Germany). 2014;92(8):889–900.CrossRef
67.
go back to reference Salemi S, Yousefi S, Constantinescu MA, Fey MF, Simon HU. Autophagy is required for self-renewal and differentiation of adult human stem cells. Cell Res. 2012;22(2):432–5.PubMedCrossRef Salemi S, Yousefi S, Constantinescu MA, Fey MF, Simon HU. Autophagy is required for self-renewal and differentiation of adult human stem cells. Cell Res. 2012;22(2):432–5.PubMedCrossRef
68.
go back to reference Oliver L, Hue E, Priault M, Vallette FM. Basal autophagy decreased during the differentiation of human adult mesenchymal stem cells. Stem Cells Dev. 2012;21(15):2779–88.PubMedCrossRef Oliver L, Hue E, Priault M, Vallette FM. Basal autophagy decreased during the differentiation of human adult mesenchymal stem cells. Stem Cells Dev. 2012;21(15):2779–88.PubMedCrossRef
69.
go back to reference Cojoc M, Mabert K, Muders MH, Dubrovska A. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. Semin Cancer Biol. 2015;31:16–27.PubMedCrossRef Cojoc M, Mabert K, Muders MH, Dubrovska A. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms. Semin Cancer Biol. 2015;31:16–27.PubMedCrossRef
70.
go back to reference Gomes LC, Scorrano L. Mitochondrial morphology in mitophagy and macroautophagy. Biochim Biophys Acta. 2013;1833(1):205–12.PubMedCrossRef Gomes LC, Scorrano L. Mitochondrial morphology in mitophagy and macroautophagy. Biochim Biophys Acta. 2013;1833(1):205–12.PubMedCrossRef
71.
go back to reference Mitani M, Yamanishi T, Miyazaki Y, Otake N. Salinomycin effects on mitochondrial ion translocation and respiration. Antimicrob Agents Chemother. 1976;9(4):655–60.PubMedPubMedCentralCrossRef Mitani M, Yamanishi T, Miyazaki Y, Otake N. Salinomycin effects on mitochondrial ion translocation and respiration. Antimicrob Agents Chemother. 1976;9(4):655–60.PubMedPubMedCentralCrossRef
72.
go back to reference Kim KY, Yu SN, Lee SY, Chun SS, Choi YL, Park YM, Song CS, Chatterjee B, Ahn SC. Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization. Biochem Biophys Res Commun. 2011;413(1):80–6.PubMedCrossRef Kim KY, Yu SN, Lee SY, Chun SS, Choi YL, Park YM, Song CS, Chatterjee B, Ahn SC. Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization. Biochem Biophys Res Commun. 2011;413(1):80–6.PubMedCrossRef
73.
go back to reference Kim KY, Park KI, Kim SH, Yu SN, Lee D, Kim YW, Noh KT, Ma JY, Seo YK, Ahn SC. Salinomycin induces reactive oxygen species and apoptosis in aggressive breast cancer cells as mediated with regulation of autophagy. Anticancer Res. 2017;37(4):1747–58.PubMedCrossRef Kim KY, Park KI, Kim SH, Yu SN, Lee D, Kim YW, Noh KT, Ma JY, Seo YK, Ahn SC. Salinomycin induces reactive oxygen species and apoptosis in aggressive breast cancer cells as mediated with regulation of autophagy. Anticancer Res. 2017;37(4):1747–58.PubMedCrossRef
74.
go back to reference Kim KY, Park KI, Kim SH, Yu SN, Park SG, Kim YW, Seo YK, Ma JY, Ahn SC. Inhibition of autophagy promotes Salinomycin-induced apoptosis via reactive oxygen species-mediated PI3K/AKT/mTOR and ERK/p38 MAPK-dependent signaling in human prostate cancer cells. Int J Mol Sci. 2017;18(5) Kim KY, Park KI, Kim SH, Yu SN, Park SG, Kim YW, Seo YK, Ma JY, Ahn SC. Inhibition of autophagy promotes Salinomycin-induced apoptosis via reactive oxygen species-mediated PI3K/AKT/mTOR and ERK/p38 MAPK-dependent signaling in human prostate cancer cells. Int J Mol Sci. 2017;18(5)
75.
go back to reference Yu SN, Kim SH, Kim KY, Ji JH, Seo YK, Yu HS, Ahn SC. Salinomycin induces endoplasmic reticulum stress mediated autophagy and apoptosis through generation of reactive oxygen species in human glioma U87MG cells. Oncol Rep. 2017; Yu SN, Kim SH, Kim KY, Ji JH, Seo YK, Yu HS, Ahn SC. Salinomycin induces endoplasmic reticulum stress mediated autophagy and apoptosis through generation of reactive oxygen species in human glioma U87MG cells. Oncol Rep. 2017;
76.
go back to reference Kim GD, Oh J, Park HJ, Bae K, Lee SK. Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Int J Oncol. 2013;43(2):600–10.PubMedCrossRef Kim GD, Oh J, Park HJ, Bae K, Lee SK. Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Int J Oncol. 2013;43(2):600–10.PubMedCrossRef
77.
go back to reference Ji C, Yang YL, Yang Z, Tu Y, Cheng L, Chen B, Xia JP, Sun WL, Su ZL, He L, et al. Perifosine sensitizes UVB-induced apoptosis in skin cells: new implication of skin cancer prevention? Cell Signal. 2012;24(9):1781–9.PubMedCrossRef Ji C, Yang YL, Yang Z, Tu Y, Cheng L, Chen B, Xia JP, Sun WL, Su ZL, He L, et al. Perifosine sensitizes UVB-induced apoptosis in skin cells: new implication of skin cancer prevention? Cell Signal. 2012;24(9):1781–9.PubMedCrossRef
78.
go back to reference Rubio N, Verrax J, Dewaele M, Verfaillie T, Johansen T, Piette J, Agostinis P. p38(MAPK)-regulated induction of p62 and NBR1 after photodynamic therapy promotes autophagic clearance of ubiquitin aggregates and reduces reactive oxygen species levels by supporting Nrf2-antioxidant signaling. Free Radic Biol Med. 2014;67:292–303.PubMedCrossRef Rubio N, Verrax J, Dewaele M, Verfaillie T, Johansen T, Piette J, Agostinis P. p38(MAPK)-regulated induction of p62 and NBR1 after photodynamic therapy promotes autophagic clearance of ubiquitin aggregates and reduces reactive oxygen species levels by supporting Nrf2-antioxidant signaling. Free Radic Biol Med. 2014;67:292–303.PubMedCrossRef
79.
go back to reference Buel GR, Blenis J. CELL SIGNALING. Seeing mTORC1 specificity. Science (New York, NY). 2016;351(6268):25–6.CrossRef Buel GR, Blenis J. CELL SIGNALING. Seeing mTORC1 specificity. Science (New York, NY). 2016;351(6268):25–6.CrossRef
81.
go back to reference Sun J, Liu Y, Tran J, O'Neal P, Baudry M, Bi X. mTORC1-S6K1 inhibition or mTORC2 activation improves hippocampal synaptic plasticity and learning in Angelman syndrome mice. Cellular and molecular life sciences : CMLS. 2016;73(22):4303–14.PubMedPubMedCentralCrossRef Sun J, Liu Y, Tran J, O'Neal P, Baudry M, Bi X. mTORC1-S6K1 inhibition or mTORC2 activation improves hippocampal synaptic plasticity and learning in Angelman syndrome mice. Cellular and molecular life sciences : CMLS. 2016;73(22):4303–14.PubMedPubMedCentralCrossRef
82.
go back to reference Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;169(2):361–71.PubMedCrossRef Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;169(2):361–71.PubMedCrossRef
84.
go back to reference Jangamreddy JR, Jain MV, Hallbeck AL, Roberg K, Lotfi K, Los MJ. Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death. Oncotarget. 2015;6(12):10134–45.PubMedPubMedCentralCrossRef Jangamreddy JR, Jain MV, Hallbeck AL, Roberg K, Lotfi K, Los MJ. Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death. Oncotarget. 2015;6(12):10134–45.PubMedPubMedCentralCrossRef
86.
go back to reference Kim J, Kim YC, Fang C, Russell RC, Kim JH, Fan W, Liu R, Zhong Q, Guan KL. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152(1–2):290–303.PubMedPubMedCentralCrossRef Kim J, Kim YC, Fang C, Russell RC, Kim JH, Fan W, Liu R, Zhong Q, Guan KL. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152(1–2):290–303.PubMedPubMedCentralCrossRef
87.
go back to reference Howell JJ, Hellberg K, Turner M, Talbott G, Kolar MJ, Ross DS, Hoxhaj G, Saghatelian A, Shaw RJ, Manning BD. Metformin inhibits hepatic mTORC1 signaling via dose-dependent mechanisms involving AMPK and the TSC complex. Cell Metab. 2017;25(2):463–71.PubMedPubMedCentralCrossRef Howell JJ, Hellberg K, Turner M, Talbott G, Kolar MJ, Ross DS, Hoxhaj G, Saghatelian A, Shaw RJ, Manning BD. Metformin inhibits hepatic mTORC1 signaling via dose-dependent mechanisms involving AMPK and the TSC complex. Cell Metab. 2017;25(2):463–71.PubMedPubMedCentralCrossRef
88.
go back to reference Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006;126(5):955–68.PubMedCrossRef Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006;126(5):955–68.PubMedCrossRef
90.
go back to reference Wei Y, An Z, Zou Z, Sumpter R, Su M, Zang X, Sinha S, Gaestel M, Levine B. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. elife. 2015;4 Wei Y, An Z, Zou Z, Sumpter R, Su M, Zang X, Sinha S, Gaestel M, Levine B. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. elife. 2015;4
91.
go back to reference Zhou YY, Li Y, Jiang WQ, Zhou LF. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep. 2015;35(3) Zhou YY, Li Y, Jiang WQ, Zhou LF. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep. 2015;35(3)
92.
go back to reference Temkin V, Karin M. From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odyssey. Immunol Rev. 2007;220:8–21.PubMedCrossRef Temkin V, Karin M. From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odyssey. Immunol Rev. 2007;220:8–21.PubMedCrossRef
93.
go back to reference Takeda K, Matsuzawa A, Nishitoh H, Ichijo H. Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct. 2003;28(1):23–9.PubMedCrossRef Takeda K, Matsuzawa A, Nishitoh H, Ichijo H. Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct. 2003;28(1):23–9.PubMedCrossRef
94.
go back to reference Wong CH, Iskandar KB, Yadav SK, Hirpara JL, Loh T, Pervaiz S. Correction: simultaneous induction of non-canonical autophagy and apoptosis in cancer cells by ROS-dependent ERK and JNK activation. PLoS One. 2016;11(7):e0159352.PubMedPubMedCentralCrossRef Wong CH, Iskandar KB, Yadav SK, Hirpara JL, Loh T, Pervaiz S. Correction: simultaneous induction of non-canonical autophagy and apoptosis in cancer cells by ROS-dependent ERK and JNK activation. PLoS One. 2016;11(7):e0159352.PubMedPubMedCentralCrossRef
95.
go back to reference Zhou F, Yang Y, Xing D. Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. FEBS J. 2011;278(3):403–13.PubMedCrossRef Zhou F, Yang Y, Xing D. Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. FEBS J. 2011;278(3):403–13.PubMedCrossRef
96.
go back to reference Yla-Anttila P, Vihinen H, Jokitalo E, Eskelinen EL. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy. 2009;5(8):1180–5.PubMedCrossRef Yla-Anttila P, Vihinen H, Jokitalo E, Eskelinen EL. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy. 2009;5(8):1180–5.PubMedCrossRef
97.
go back to reference Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, et al. Autophagosomes form at ER-mitochondria contact sites. Nature. 2013;495(7441):389–93.PubMedCrossRef Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, et al. Autophagosomes form at ER-mitochondria contact sites. Nature. 2013;495(7441):389–93.PubMedCrossRef
98.
go back to reference Milani M, Rzymski T, Mellor HR, Pike L, Bottini A, Generali D, Harris AL. The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib. Cancer Res. 2009;69(10):4415–23.PubMedCrossRef Milani M, Rzymski T, Mellor HR, Pike L, Bottini A, Generali D, Harris AL. The role of ATF4 stabilization and autophagy in resistance of breast cancer cells treated with Bortezomib. Cancer Res. 2009;69(10):4415–23.PubMedCrossRef
100.
go back to reference Salazar M, Carracedo A, Salanueva IJ, Hernandez-Tiedra S, Lorente M, Egia A, Vazquez P, Blazquez C, Torres S, Garcia S, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009;119(5):1359–72.PubMedPubMedCentralCrossRef Salazar M, Carracedo A, Salanueva IJ, Hernandez-Tiedra S, Lorente M, Egia A, Vazquez P, Blazquez C, Torres S, Garcia S, et al. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009;119(5):1359–72.PubMedPubMedCentralCrossRef
101.
go back to reference Jin Y, Chen Y, Zhao S, Guan KL, Zhuang Y, Zhou W, Wu X, Xu T. DNA-PK facilitates piggyBac transposition by promoting paired-end complex formation. Proc Natl Acad Sci U S A. 2017;114(28):7408–13.PubMedPubMedCentralCrossRef Jin Y, Chen Y, Zhao S, Guan KL, Zhuang Y, Zhou W, Wu X, Xu T. DNA-PK facilitates piggyBac transposition by promoting paired-end complex formation. Proc Natl Acad Sci U S A. 2017;114(28):7408–13.PubMedPubMedCentralCrossRef
102.
go back to reference Falck J, Coates J, Jackson SP. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005;434(7033):605–11.PubMedCrossRef Falck J, Coates J, Jackson SP. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005;434(7033):605–11.PubMedCrossRef
103.
go back to reference Kaplan F, Teksen F. Apoptotic effects of salinomycin on human ovarian cancer cell line (OVCAR-3). Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37(3):3897–903.CrossRef Kaplan F, Teksen F. Apoptotic effects of salinomycin on human ovarian cancer cell line (OVCAR-3). Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37(3):3897–903.CrossRef
104.
go back to reference Qin LS, Jia PF, Zhang ZQ, Zhang SM. ROS-p53-cyclophilin-D signaling mediates salinomycin-induced glioma cell necrosis. Journal of experimental & clinical cancer research : CR. 2015;34:57.PubMedCentralCrossRef Qin LS, Jia PF, Zhang ZQ, Zhang SM. ROS-p53-cyclophilin-D signaling mediates salinomycin-induced glioma cell necrosis. Journal of experimental & clinical cancer research : CR. 2015;34:57.PubMedCentralCrossRef
105.
go back to reference Tang QL, Zhao ZQ, Li JC, Liang Y, Yin JQ, Zou CY, Xie XB, Zeng YX, Shen JN, Kang T, et al. Salinomycin inhibits osteosarcoma by targeting its tumor stem cells. Cancer Lett. 2011;311(1):113–21.PubMedCrossRef Tang QL, Zhao ZQ, Li JC, Liang Y, Yin JQ, Zou CY, Xie XB, Zeng YX, Shen JN, Kang T, et al. Salinomycin inhibits osteosarcoma by targeting its tumor stem cells. Cancer Lett. 2011;311(1):113–21.PubMedCrossRef
106.
go back to reference Arafat K, Iratni R, Takahashi T, Parekh K, Al Dhaheri Y, Adrian TE, Attoub S. Inhibitory effects of Salinomycin on cell survival, Colony growth, migration, and invasion of human non-small cell lung cancer A549 and LNM35: involvement of NAG-1. PLoS One. 2013;8(6):e66931.PubMedPubMedCentralCrossRef Arafat K, Iratni R, Takahashi T, Parekh K, Al Dhaheri Y, Adrian TE, Attoub S. Inhibitory effects of Salinomycin on cell survival, Colony growth, migration, and invasion of human non-small cell lung cancer A549 and LNM35: involvement of NAG-1. PLoS One. 2013;8(6):e66931.PubMedPubMedCentralCrossRef
107.
go back to reference Al Dhaheri Y, Attoub S, Arafat K, Abuqamar S, Eid A, Al Faresi N, Iratni R. Salinomycin induces apoptosis and senescence in breast cancer: upregulation of p21, downregulation of survivin and histone H3 and H4 hyperacetylation. Biochim Biophys Acta. 2013;1830(4):3121–35.PubMedCrossRef Al Dhaheri Y, Attoub S, Arafat K, Abuqamar S, Eid A, Al Faresi N, Iratni R. Salinomycin induces apoptosis and senescence in breast cancer: upregulation of p21, downregulation of survivin and histone H3 and H4 hyperacetylation. Biochim Biophys Acta. 2013;1830(4):3121–35.PubMedCrossRef
108.
go back to reference Shen HM, Codogno P. Autophagic cell death: loch ness monster or endangered species? Autophagy. 2011;7(5):457–65.PubMedCrossRef Shen HM, Codogno P. Autophagic cell death: loch ness monster or endangered species? Autophagy. 2011;7(5):457–65.PubMedCrossRef
109.
go back to reference Thorburn A. Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis : an international journal on programmed cell death. 2008;13(1):1–9.CrossRef Thorburn A. Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis : an international journal on programmed cell death. 2008;13(1):1–9.CrossRef
110.
111.
go back to reference Egan D, Kim J, Shaw RJ, Guan KL. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy. 2011;7(6):643–4.PubMedCrossRef Egan D, Kim J, Shaw RJ, Guan KL. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy. 2011;7(6):643–4.PubMedCrossRef
112.
go back to reference Lee JH, Won YS, Park KH, Lee MK, Tachibana H, Yamada K, Seo KI. Celastrol inhibits growth and induces apoptotic cell death in melanoma cells via the activation ROS-dependent mitochondrial pathway and the suppression of PI3K/AKT signaling. Apoptosis : an international journal on programmed cell death. 2012;17(12):1275–86.CrossRef Lee JH, Won YS, Park KH, Lee MK, Tachibana H, Yamada K, Seo KI. Celastrol inhibits growth and induces apoptotic cell death in melanoma cells via the activation ROS-dependent mitochondrial pathway and the suppression of PI3K/AKT signaling. Apoptosis : an international journal on programmed cell death. 2012;17(12):1275–86.CrossRef
113.
go back to reference Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005;120(5):649–61.PubMedCrossRef Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005;120(5):649–61.PubMedCrossRef
Metadata
Title
Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review
Authors
Jiang Jiang
Hailong Li
Eskandar Qaed
Jing Zhang
Yushu Song
Rong Wu
Xinmiao Bu
Qinyan Wang
Zeyao Tang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0680-z

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