Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

Synergistic inhibitory effects of capsaicin combined with cisplatin on human osteosarcoma in culture and in xenografts

Authors: Yang Wang, Xu Deng, Chang Yu, Guosheng Zhao, Jing Zhou, Ge Zhang, Ming Li, Dianming Jiang, Zhengxue Quan, Yuan Zhang

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

Login to get access

Abstract

Background

The combination of phytochemicals with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses.

Methods

The present study investigates the effect of the combination of capsaicin (CAP) with cisplatin (DDP) and the potential underlying anticancer mechanisms in osteosarcoma (OS) cells in vitro and in vivo.

Results

Cell viability assays and isobolographic analyses demonstrated that the combination of CAP and DDP showed synergistic cytotoxic effects on OS cells. We chose relatively low concentrations of CAP (100 μM) and DDP (16.7 μM) for subsequent experiments. Generally, the combination of CAP and DDP had significant effects on apoptosis induction, cell cycle arrest and cell invasion inhibition in OS cells compared with the individual-treatment groups and the control group. Moreover, cotreatment with CAP and DDP triggered prosurvival autophagy through reactive oxygen species (ROS)/JNK and p-AKT/mTOR signaling in OS cells. The combination regimen of CAP and DDP also inhibited tumor growth in an OS xenograft model.

Conclusion

These results suggest that the combination of CAP and DDP has strong inhibitory effects on OS cells and identify CAP as a promising agent for supplementing standard chemotherapy and possible future targeted therapy in OS.
Literature
1.
go back to reference Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33(27):3029–35.CrossRef Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33(27):3029–35.CrossRef
2.
go back to reference Jaffe N, Puri A, Gelderblom H. Osteosarcoma: evolution of treatment paradigms. Sarcoma. 2013;2013:203531.CrossRef Jaffe N, Puri A, Gelderblom H. Osteosarcoma: evolution of treatment paradigms. Sarcoma. 2013;2013:203531.CrossRef
3.
go back to reference Gaetano Bacci MD, Michele Rocca MD, MariaCristina Salone MD, Alba Balladelli BA, Stefano Ferrari MD, et al. High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions. J Surg Oncol. 2008;98(6):415–20.CrossRef Gaetano Bacci MD, Michele Rocca MD, MariaCristina Salone MD, Alba Balladelli BA, Stefano Ferrari MD, et al. High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions. J Surg Oncol. 2008;98(6):415–20.CrossRef
4.
go back to reference Ferreira JA, Peixoto A, Neves M, Gaiteiro C, Reis CA, et al. Mechanisms of cisplatin resistance and targeting of cancer stem cells: adding glycosylation to the equation. Drug Resist Updat. 2016;24:34–54.CrossRef Ferreira JA, Peixoto A, Neves M, Gaiteiro C, Reis CA, et al. Mechanisms of cisplatin resistance and targeting of cancer stem cells: adding glycosylation to the equation. Drug Resist Updat. 2016;24:34–54.CrossRef
5.
go back to reference Bramwell VH, Steward WP, Nooij M, Whelan J, Craft AW, et al. Neoadjuvant chemotherapy with doxorubicin and cisplatin in malignant fibrous histiocytoma of bone: a European osteosarcoma intergroup study. J Clin Oncol. 1999;17(10):3260–9.CrossRef Bramwell VH, Steward WP, Nooij M, Whelan J, Craft AW, et al. Neoadjuvant chemotherapy with doxorubicin and cisplatin in malignant fibrous histiocytoma of bone: a European osteosarcoma intergroup study. J Clin Oncol. 1999;17(10):3260–9.CrossRef
6.
go back to reference Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364–78.CrossRef Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364–78.CrossRef
7.
go back to reference Lin F, Wang Q, Yu W, Tang L, Zheng S, et al. Clinical analysis of Chinese limb osteosarcoma patients treated by two combinations of methotrexate, cisplatin, doxorubicin and ifosfamide. Asia Pac J Clin Oncol. 2011;7(3):270–5.CrossRef Lin F, Wang Q, Yu W, Tang L, Zheng S, et al. Clinical analysis of Chinese limb osteosarcoma patients treated by two combinations of methotrexate, cisplatin, doxorubicin and ifosfamide. Asia Pac J Clin Oncol. 2011;7(3):270–5.CrossRef
8.
go back to reference Igarashi K, Yamamoto N, Hayashi K, Takeuchi K, Miwa S, Odani A, et al. Effectiveness of two novel anionic and cationic platinum complexes in the treatment of osteosarcoma. Anti Cancer Agents Med Chem. 2015;15:390–9.CrossRef Igarashi K, Yamamoto N, Hayashi K, Takeuchi K, Miwa S, Odani A, et al. Effectiveness of two novel anionic and cationic platinum complexes in the treatment of osteosarcoma. Anti Cancer Agents Med Chem. 2015;15:390–9.CrossRef
9.
go back to reference León IE, Cadavidvargas JF, Resasco A, Maschi F, Ayala MA, Carbone C, et al. In vitro and in vivo antitumor effects of the vo-chrysin complex on a new three-dimensional osteosarcoma spheroids model and a xenograft tumor in mice. J Biol Inorg Chem. 21(8):1–12.CrossRef León IE, Cadavidvargas JF, Resasco A, Maschi F, Ayala MA, Carbone C, et al. In vitro and in vivo antitumor effects of the vo-chrysin complex on a new three-dimensional osteosarcoma spheroids model and a xenograft tumor in mice. J Biol Inorg Chem. 21(8):1–12.CrossRef
10.
go back to reference León IE, Butenko N, Di VA, Muglia CI, Baran EJ, Cavaco I, et al. Vanadium and cancer treatment: antitumoral mechanisms of three oxidovanadium(iv) complexes on a human osteosarcoma cell line. J Inorg Biochem. 134(3):106–17.CrossRef León IE, Butenko N, Di VA, Muglia CI, Baran EJ, Cavaco I, et al. Vanadium and cancer treatment: antitumoral mechanisms of three oxidovanadium(iv) complexes on a human osteosarcoma cell line. J Inorg Biochem. 134(3):106–17.CrossRef
11.
go back to reference Kandikattu HK, Rachitha P, Jayashree GV, Krupashree K, Sukhith M, et al. Anti-inflammatory and anti-oxidant effects of cardamom (Elettaria repens (Sonn.) Baill) and its phytochemical analysis by 4D GCXGC TOF-MS. Biomed Pharmacother. 2017;91:191–201.CrossRef Kandikattu HK, Rachitha P, Jayashree GV, Krupashree K, Sukhith M, et al. Anti-inflammatory and anti-oxidant effects of cardamom (Elettaria repens (Sonn.) Baill) and its phytochemical analysis by 4D GCXGC TOF-MS. Biomed Pharmacother. 2017;91:191–201.CrossRef
12.
go back to reference Harakeh S, Khan I, Almasaudi SB, Azhar EI, Aljaouni S, et al. Role of nutrients and Phyto-compounds in the modulation of antimicrobial resistance. Curr Drug Metab. 2017;18(9):858–67.CrossRef Harakeh S, Khan I, Almasaudi SB, Azhar EI, Aljaouni S, et al. Role of nutrients and Phyto-compounds in the modulation of antimicrobial resistance. Curr Drug Metab. 2017;18(9):858–67.CrossRef
13.
go back to reference Liu Z, Zhai J, Han N, Yin J. Assessment of anti-diabetic activity of the aqueous extract of leaves of Astilboides tabularis. J Ethnopharmacol. 2016;194:635–41.CrossRef Liu Z, Zhai J, Han N, Yin J. Assessment of anti-diabetic activity of the aqueous extract of leaves of Astilboides tabularis. J Ethnopharmacol. 2016;194:635–41.CrossRef
14.
go back to reference Mbiantcha M, Almas J, Dawe A, Faheem A, Sidra Z. Analgesic, anti-inflammatory and anticancer activities of Combretin A and Combretin B isolated from Combretum fragrans F. HOFFM (Combretaceae) leaves. Inflammopharmacology. 2017;1:1–12. Mbiantcha M, Almas J, Dawe A, Faheem A, Sidra Z. Analgesic, anti-inflammatory and anticancer activities of Combretin A and Combretin B isolated from Combretum fragrans F. HOFFM (Combretaceae) leaves. Inflammopharmacology. 2017;1:1–12.
15.
go back to reference Dayem AA, Choi HY, Yang GM, Kim K, Saha SK, et al. The anti-Cancer effect of polyphenols against breast Cancer and Cancer stem cells: molecular mechanisms. Nutrients. 2016;8(9):581.CrossRef Dayem AA, Choi HY, Yang GM, Kim K, Saha SK, et al. The anti-Cancer effect of polyphenols against breast Cancer and Cancer stem cells: molecular mechanisms. Nutrients. 2016;8(9):581.CrossRef
16.
go back to reference Fu Y, Chang H, Peng X, Bai Q, Yi L, et al. Resveratrol inhibits breast cancer stem-like cells and induces autophagy via suppressing Wnt/β-catenin signaling pathway. PLoS One. 2014;9(7):e102535.CrossRef Fu Y, Chang H, Peng X, Bai Q, Yi L, et al. Resveratrol inhibits breast cancer stem-like cells and induces autophagy via suppressing Wnt/β-catenin signaling pathway. PLoS One. 2014;9(7):e102535.CrossRef
17.
go back to reference Gali-Muhtasib H, Hmadi R, Kareh M, Tohme R, Darwiche N. Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. Apoptosis. 2015;20(12):1531.CrossRef Gali-Muhtasib H, Hmadi R, Kareh M, Tohme R, Darwiche N. Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. Apoptosis. 2015;20(12):1531.CrossRef
18.
go back to reference Li X, Huang T, Jiang G, Gong W, Qian H, et al. Synergistic apoptotic effect of crocin and cisplatin on osteosarcoma cells via caspase induced apoptosis. Toxicol Lett. 2013;221(3):197–204.CrossRef Li X, Huang T, Jiang G, Gong W, Qian H, et al. Synergistic apoptotic effect of crocin and cisplatin on osteosarcoma cells via caspase induced apoptosis. Toxicol Lett. 2013;221(3):197–204.CrossRef
19.
go back to reference Najafzadeh N, Mazani M, Abbasi A, Farassati F, Amani M. Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44(+) cancer stem cells. Biomed Pharmacother. 2015;74:243–51.CrossRef Najafzadeh N, Mazani M, Abbasi A, Farassati F, Amani M. Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44(+) cancer stem cells. Biomed Pharmacother. 2015;74:243–51.CrossRef
20.
go back to reference Huang Z, Yang G, Shen T, Wang X, Li H, et al. Dehydrobruceine B enhances the cisplatin-induced cytotoxicity through regulation of the mitochondrial apoptotic pathway in lung cancer A549 cells. Biomed Pharmacother. 2017;89:623–31.CrossRef Huang Z, Yang G, Shen T, Wang X, Li H, et al. Dehydrobruceine B enhances the cisplatin-induced cytotoxicity through regulation of the mitochondrial apoptotic pathway in lung cancer A549 cells. Biomed Pharmacother. 2017;89:623–31.CrossRef
21.
go back to reference Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA. Capsaicin: current understanding of its mechanisms and therapy of pain and other pre-clinical and clinical uses. Molecules. 2016;28:21(7). Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA. Capsaicin: current understanding of its mechanisms and therapy of pain and other pre-clinical and clinical uses. Molecules. 2016;28:21(7).
22.
go back to reference Bley K, Boorman G, Mohammad B, Mckenzie D, Babbar S. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40(6):847–73.CrossRef Bley K, Boorman G, Mohammad B, Mckenzie D, Babbar S. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol Pathol. 2012;40(6):847–73.CrossRef
23.
go back to reference Zhang Y, Deng X, Lei T, Yu C, Wang Y, et al. Capsaicin inhibits proliferation and induces apoptosis in osteosarcoma cell lines via the mitogen‑activated protein kinase pathway. Oncol Rep. 2017;38(5):2685–96.CrossRef Zhang Y, Deng X, Lei T, Yu C, Wang Y, et al. Capsaicin inhibits proliferation and induces apoptosis in osteosarcoma cell lines via the mitogen‑activated protein kinase pathway. Oncol Rep. 2017;38(5):2685–96.CrossRef
24.
go back to reference Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440–6.CrossRef Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440–6.CrossRef
25.
go back to reference Chikara S, Nagaprashantha LD, Singhal J, Horne D, Awasthi S, et al. Oxidative stress and dietary phytochemicals: role in cancer chemoprevention and treatment. Cancer Lett. 2018;413:122–34.CrossRef Chikara S, Nagaprashantha LD, Singhal J, Horne D, Awasthi S, et al. Oxidative stress and dietary phytochemicals: role in cancer chemoprevention and treatment. Cancer Lett. 2018;413:122–34.CrossRef
26.
go back to reference Shukla S, Meeran SM, Katiyar SK. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer Lett. 2014;355(1):9–17.CrossRef Shukla S, Meeran SM, Katiyar SK. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer Lett. 2014;355(1):9–17.CrossRef
27.
go back to reference Huang T, Gong W, Li X, Zou C, Jiang G, et al. Enhancement of osteosarcoma cell sensitivity to cisplatin using paclitaxel in the presence of hyperthermia. Int J Hyperth. 2013;29(3):248–55.CrossRef Huang T, Gong W, Li X, Zou C, Jiang G, et al. Enhancement of osteosarcoma cell sensitivity to cisplatin using paclitaxel in the presence of hyperthermia. Int J Hyperth. 2013;29(3):248–55.CrossRef
28.
go back to reference Jung SH, Kim HJ, Oh GS, Shen AH, Lee S, et al. Capsaicin ameliorates cisplatin-induced renal injury through induction of Heme Oxygenase-1. Mol Cells. 2014;37(3):234–40.CrossRef Jung SH, Kim HJ, Oh GS, Shen AH, Lee S, et al. Capsaicin ameliorates cisplatin-induced renal injury through induction of Heme Oxygenase-1. Mol Cells. 2014;37(3):234–40.CrossRef
29.
go back to reference Ledgerwood EC, Morison IM. Targeting the apoptosome for cancer therapy. Clin Cancer Res. 2009;15(2):420–4.CrossRef Ledgerwood EC, Morison IM. Targeting the apoptosome for cancer therapy. Clin Cancer Res. 2009;15(2):420–4.CrossRef
30.
go back to reference PrietoVila M, Takahashi R, Usuba W, Kohama I, Ochiya T. Drug resistance driven by Cancer stem cells and their niche. Int J Mol Sci. 2017;1:18(12). PrietoVila M, Takahashi R, Usuba W, Kohama I, Ochiya T. Drug resistance driven by Cancer stem cells and their niche. Int J Mol Sci. 2017;1:18(12).
31.
go back to reference Leung EL, Fraser M, Fiscus RR, Tsang BK. Cisplatin alters nitric oxide synthase levels in human ovarian cancer cells: involvement in p53 regulation and cisplatin resistance. Br J Cancer. 2008;98(11):1803–9.CrossRef Leung EL, Fraser M, Fiscus RR, Tsang BK. Cisplatin alters nitric oxide synthase levels in human ovarian cancer cells: involvement in p53 regulation and cisplatin resistance. Br J Cancer. 2008;98(11):1803–9.CrossRef
32.
go back to reference Hensley P, Mishra M, Kyprianou N. Targeting caspases in cancer therapeutics. Biol Chem. 2013;394(7):831–43.CrossRef Hensley P, Mishra M, Kyprianou N. Targeting caspases in cancer therapeutics. Biol Chem. 2013;394(7):831–43.CrossRef
33.
go back to reference Skrzypski M, Sassek M, Abdelmessih S, Mergler S, Grötzinger C, et al. Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action. Cell Signal. 2014;26(1):41–8.CrossRef Skrzypski M, Sassek M, Abdelmessih S, Mergler S, Grötzinger C, et al. Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action. Cell Signal. 2014;26(1):41–8.CrossRef
34.
go back to reference Engeland K. Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM. Cell Death Differ. 2018;25(1):114–32.CrossRef Engeland K. Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM. Cell Death Differ. 2018;25(1):114–32.CrossRef
35.
go back to reference De AG, Kuijpers CJ, Kroep JR. CDK4/6 inhibition in early and metastatic breast cancer: a review. Cancer Treat Rev. 2017;60:130–8.CrossRef De AG, Kuijpers CJ, Kroep JR. CDK4/6 inhibition in early and metastatic breast cancer: a review. Cancer Treat Rev. 2017;60:130–8.CrossRef
36.
go back to reference Lin S, Shang Z, Li S, Gao P, Zhang Y, et al. Neddylation inhibitor MLN4924 induces G2 cell cycle arrest, DNA damage and sensitizes esophageal squamous cell carcinoma cells to cisplatin. Oncol Lett. 2018;15(2):2583–9.PubMed Lin S, Shang Z, Li S, Gao P, Zhang Y, et al. Neddylation inhibitor MLN4924 induces G2 cell cycle arrest, DNA damage and sensitizes esophageal squamous cell carcinoma cells to cisplatin. Oncol Lett. 2018;15(2):2583–9.PubMed
37.
go back to reference Horvath Z, Marihart-Fazekas S, Saiko P, Grusch M, Ozsüy M, et al. Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines. Anticancer Res. 2007;27(5A):3459–64.PubMed Horvath Z, Marihart-Fazekas S, Saiko P, Grusch M, Ozsüy M, et al. Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines. Anticancer Res. 2007;27(5A):3459–64.PubMed
38.
go back to reference Yang Q, Zhang S, Kang M, Dong R, Zhao J. Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells. Oncol Rep. 2015;33(5):2537–44.CrossRef Yang Q, Zhang S, Kang M, Dong R, Zhao J. Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells. Oncol Rep. 2015;33(5):2537–44.CrossRef
39.
go back to reference Zhao W, You CC, Zhuang JP, Zu JN, Chi ZY, et al. Viability inhibition effect of gambogic acid combined with cisplatin on osteosarcoma cells via mitochondria-independent apoptotic pathway. Mol Cell Biochem. 2013;382(1–2):243–52.PubMed Zhao W, You CC, Zhuang JP, Zu JN, Chi ZY, et al. Viability inhibition effect of gambogic acid combined with cisplatin on osteosarcoma cells via mitochondria-independent apoptotic pathway. Mol Cell Biochem. 2013;382(1–2):243–52.PubMed
40.
go back to reference Mlecnik B, Bindea G, Kirilovsky A, Angell HK, Obenauf AC, et al. The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Sci Transl Med. 2016;8(327):327ra26.CrossRef Mlecnik B, Bindea G, Kirilovsky A, Angell HK, Obenauf AC, et al. The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Sci Transl Med. 2016;8(327):327ra26.CrossRef
41.
go back to reference H S TT, Y O JC, A S EY, et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994;370(6484):61–5.CrossRef H S TT, Y O JC, A S EY, et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994;370(6484):61–5.CrossRef
42.
go back to reference Cheng G, Gao F, Sun X, Bi H, Zhu Y. Paris saponin VII suppresses osteosarcoma cell migration and invasion by inhibiting MMP-2/9 production via the p38 MAPK signaling pathway. Mol Med Rep. 2016;14(4):3199–205.CrossRef Cheng G, Gao F, Sun X, Bi H, Zhu Y. Paris saponin VII suppresses osteosarcoma cell migration and invasion by inhibiting MMP-2/9 production via the p38 MAPK signaling pathway. Mol Med Rep. 2016;14(4):3199–205.CrossRef
43.
go back to reference Hwang YP, Yun HJ, Choi JH, Han EH, Kim HG, et al. Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling. Mol Nutr Food Res. 2011;55(4):594–605.CrossRef Hwang YP, Yun HJ, Choi JH, Han EH, Kim HG, et al. Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling. Mol Nutr Food Res. 2011;55(4):594–605.CrossRef
44.
go back to reference Lee GR, Jang SH, Chang JK, Kim AR, Yoon DJ, et al. Capsaicin suppresses the migration of cholangiocarcinoma cells by down-regulating matrix metalloproteinase-9 expression via the AMPK–NF-κB signaling pathway. Clin Exp Metastasis. 2014;31(8):897–907.CrossRef Lee GR, Jang SH, Chang JK, Kim AR, Yoon DJ, et al. Capsaicin suppresses the migration of cholangiocarcinoma cells by down-regulating matrix metalloproteinase-9 expression via the AMPK–NF-κB signaling pathway. Clin Exp Metastasis. 2014;31(8):897–907.CrossRef
45.
go back to reference Hongtao HE, Jiangdong NI, Huang J. Molecular mechanisms of chemoresistance in osteosarcoma (review). Oncol Lett. 2014;7(5):1352–62.CrossRef Hongtao HE, Jiangdong NI, Huang J. Molecular mechanisms of chemoresistance in osteosarcoma (review). Oncol Lett. 2014;7(5):1352–62.CrossRef
46.
go back to reference Singh SS, Vats S, Chia AY, Tan TZ, Deng S, et al. Dual role of autophagy in hallmarks of cancer. Oncogene. 2018;37(9):1142–58.CrossRef Singh SS, Vats S, Chia AY, Tan TZ, Deng S, et al. Dual role of autophagy in hallmarks of cancer. Oncogene. 2018;37(9):1142–58.CrossRef
47.
go back to reference Jin S, White E. Role of autophagy in cancer: management of metabolic stress. Autophagy. 2007;3(1):28–31.CrossRef Jin S, White E. Role of autophagy in cancer: management of metabolic stress. Autophagy. 2007;3(1):28–31.CrossRef
48.
go back to reference Moosavi MA, Haghi A, Rahmati M, Taniguchi H, Mocan A, et al. Phytochemicals as potent modulators of autophagy for cancer therapy. Cancer Lett. 2018;424:46–69.CrossRef Moosavi MA, Haghi A, Rahmati M, Taniguchi H, Mocan A, et al. Phytochemicals as potent modulators of autophagy for cancer therapy. Cancer Lett. 2018;424:46–69.CrossRef
49.
go back to reference K S KMK, B S RBP, WA P. Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit Rev Oncog. 2012;17(1):69–95.CrossRef K S KMK, B S RBP, WA P. Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit Rev Oncog. 2012;17(1):69–95.CrossRef
50.
go back to reference Vucicevic L, Misirkic M, Janjetovic K, Vilimanovich U, Sudar E, et al. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. Autophagy. 2011;7(1):40–50.CrossRef Vucicevic L, Misirkic M, Janjetovic K, Vilimanovich U, Sudar E, et al. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. Autophagy. 2011;7(1):40–50.CrossRef
51.
go back to reference H P DC. P H. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7(2):97–110.CrossRef H P DC. P H. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7(2):97–110.CrossRef
52.
go back to reference Wong CH, Iskandar KB, Yadav SK, Hirpara JL, Loh T, et al. Simultaneous induction of non-canonical autophagy and apoptosis in Cancer cells by ROS-dependent ERK and JNK activation. PLoS One. 2010;5(4):e9996.CrossRef Wong CH, Iskandar KB, Yadav SK, Hirpara JL, Loh T, et al. Simultaneous induction of non-canonical autophagy and apoptosis in Cancer cells by ROS-dependent ERK and JNK activation. PLoS One. 2010;5(4):e9996.CrossRef
53.
go back to reference Wu Q, Deng J, Fan D, Duan Z, Zhu C, et al. Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells. Biochem Pharmacol. 2018;148:64–74.CrossRef Wu Q, Deng J, Fan D, Duan Z, Zhu C, et al. Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells. Biochem Pharmacol. 2018;148:64–74.CrossRef
Metadata
Title
Synergistic inhibitory effects of capsaicin combined with cisplatin on human osteosarcoma in culture and in xenografts
Authors
Yang Wang
Xu Deng
Chang Yu
Guosheng Zhao
Jing Zhou
Ge Zhang
Ming Li
Dianming Jiang
Zhengxue Quan
Yuan Zhang
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/s13046-018-0922-0

Other articles of this Issue 1/2018

Journal of Experimental & Clinical Cancer Research 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine