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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Biomarkers | Review

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer

Authors: Khushbukhat Khan, Cristina Quispe, Zeeshan Javed, Muhammad Javed Iqbal, Haleema Sadia, Shahid Raza, Asma Irshad, Bahare Salehi, Željko Reiner, Javad Sharifi-Rad

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male population. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasiveness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different possible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabilities. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer.
Literature
1.
Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017;71(1):96–108.PubMedCrossRef
2.
3.
Kogevinas M. Bladder cancer. In: Occupational cancers. Berlin: Springer; 2020, p. 487–506.
4.
Wong MC, Fung FD, Leung C, Cheung WW, Goggins WB, Ng C. The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection. Sci Rep. 2018;8(1):1129.PubMedPubMedCentralCrossRef
5.
Scicinski J, Kashfi K. Cancer and beyond: discovery and development of NO-releasing therapeutics. In: Therapeutic application of nitric oxide in cancer and inflammatory disorders. Amsterdam: Elsevier; 2019. p. 123–158.
6.
Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström P-U, Choi W, Guo CC, Lotan Y, Kassouf W. Bladder cancer. Lancet. 2016;388(10061):2796–810.PubMedCrossRef
7.
Pietzak EJ, Bagrodia A, Cha EK, Drill EN, Iyer G, Isharwal S, Ostrovnaya I, Baez P, Li Q, Berger MF. Next-generation sequencing of nonmuscle invasive bladder cancer reveals potential biomarkers and rational therapeutic targets. Eur Urol. 2017;72(6):952–9.PubMedPubMedCentralCrossRef
8.
9.
David D, Abufaraj M, Susani M, Ristl R, Foerster B, Kimura S, Mari A, Soria F, Briganti A, Karakiewicz PI. Accurate prediction of progression to muscle-invasive disease in patients with pT1G3 bladder cancer: a clinical decision-making tool. Urol Oncol. 2018;36:239.e1-239.e7.CrossRef
10.
Signore M, Ricci-Vitiani L, De Maria R. Targeting apoptosis pathways in cancer stem cells. Cancer Lett. 2013;332(2):374–82.PubMedCrossRef
11.
12.
13.
14.
15.
Ciuffreda L, Di Sanza C, Incani UC, Milella M. The mTOR pathway: a new target in cancer therapy. Curr Cancer Drug Targets. 2010;10(5):484–95.PubMedCrossRef
16.
17.
18.
Guertin DA, Sabatini DM. An expanding role for mTOR in cancer. Trends Mol Med. 2005;11(8):353–61.PubMedCrossRef
19.
Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase—AKT pathway in human cancer. Nat Rev Cancer. 2002;2(7):489.PubMedCrossRef
20.
Zha X, Hu Z, He S, Wang F, Shen H, Zhang H. TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade. Cancer Lett. 2011;313(2):211–7.PubMedCrossRef
21.
Javed Z, Iqbal MZ, Latif MU, Yaqub HMF, Qadri QR. Potent implications of miRNA in cancer biology—a brief review. Adv Life Sci. 2015;2(3):106–9.
22.
Farooqi AA, Fayyaz S, Shatynska-Mytsyk I, Javed Z, Jabeen S, Yaylim I, Gasparri ML, Panici PB. Is miR-34a a well-equipped swordsman to conquer temple of molecular oncology? Chem Biol Drug Des. 2016;87(3):321–34.PubMedCrossRef
23.
Lin JF, Tsai TF, Lin YC, Chen HE, Chou KY, Hwang TI. Benzyl isothiocyanate suppresses IGF1R, FGFR3 and mTOR expression by upregulation of miR-99a-5p in human bladder cancer cells. Int J Oncol. 2019;54(6):2106–16.PubMed
24.
Salehi B, Selamoglu Z, Sener B, Kilic M, Kumar Jugran A, de Tommasi N, Sinisgalli C, Milella L, Rajkovic J, Morais-Braga FB. Berberis plants—drifting from farm to food applications, phytotherapy, and phytopharmacology. Foods. 2019;8(10):522.PubMedCentralCrossRef
25.
Salehi B, Sener B, Kilic M, Sharifi-Rad J, Naz R, Yousaf Z, Mudau FN, Fokou PVT, Ezzat SM, El Bishbishy MH. Dioscorea plants: a genus rich in vital nutra-pharmaceuticals—a review. Iran J Pharm Res. 2019;18:68–89.PubMedPubMedCentral
26.
Sharifi-Rad J, Melgar-Lalanne G, Hernández-Álvarez AJ, Taheri Y, Shaheen S, Kregiel D, Antolak H, Pawlikowska E, Brdar-Jokanović M, Rajkovic J. Malva species: insights on its chemical composition towards pharmacological applications. Phytotherapy Res. 2020;34(3):546–67.CrossRef
27.
Farooqi A, Khalid S, Ahmad A. Regulation of cell signaling pathways and miRNAs by resveratrol in different cancers. Int J Mol Sci. 2018;19(3):652.PubMedCentralCrossRef
28.
Rutz J, Janicova A, Woidacki K, Chun FKH, Blaheta RA, Relja B. Curcumin—a viable agent for better bladder cancer treatment. Int J Mol Sci. 2020;21(11):3761.PubMedCentralCrossRef
29.
Hernández-Prat A, Rodriguez-Vida A, Juanpere-Rodero N, Arpi O, Menéndez S, Soria-Jiménez L, Martínez A, Iarchouk N, Rojo F, Albanell J. Novel oral mTORC1/2 inhibitor TAK-228 has synergistic antitumor effects when combined with paclitaxel or PI3Kα inhibitor TAK-117 in preclinical bladder cancer models. Mol Cancer Res. 2019;17(9):1931–44.PubMedCrossRef
30.
Wu Y, Liu F. Targeting mTOR: evaluating the therapeutic potential of resveratrol for cancer treatment. Anti-Cancer Agents Med Chem (formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2013;13(7):1032–8.CrossRef
31.
Fonseca BD, Graber TE, Hoang H-D, González A, Soukas AA, Hernández G, Alain T, Swift SL, Weisman R, Meyer C. Evolution of TOR and translation control. In: Evolution of the protein synthesis machinery and its regulation. Berlin: Springer; 2016. p 327–411.
32.
Efeyan A, Sabatini DM. mTOR and cancer: many loops in one pathway. Curr Opin Cell Biol. 2010;22(2):169–76.PubMedCrossRef
33.
Pearce LR, Huang X, Boudeau J, Pawłowski R, Wullschleger S, Deak M, Ibrahim AF, Gourlay R, Magnuson MA, Alessi DR. Identification of protor as a novel rictor-binding component of mTOR complex-2. Biochem J. 2007;405(3):513–22.PubMedPubMedCentralCrossRef
34.
Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7(8):606.PubMedCrossRef
35.
36.
Mamane Y, Petroulakis E, LeBacquer O, Sonenberg N. mTOR, translation initiation and cancer. Oncogene. 2006;25(48):6416.PubMedCrossRef
37.
Buller CL, Loberg RD, Fan M-H, Zhu Q, Park JL, Vesely E, Inoki K, Guan K-L, Brosius FC III. A GSK-3/TSC2/mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression. Am J Physiol Cell Physiol. 2008;295(3):C836–43.PubMedPubMedCentralCrossRef
38.
Szablewski L. Expression of glucose transporters in cancers. Biochimica et Biophysica Acta (BBA)—Rev Cancer. 2013;1835(2):164–9.CrossRef
39.
Kleszcz R, Paluszczak J, Krajka-Kuźniak V, Baer-Dubowska W. The inhibition of c-MYC transcription factor modulates the expression of glycolytic and glutaminolytic enzymes in FaDu hypopharyngeal carcinoma cells. Adv Clin Exp Med. 2018;27:735–42.PubMedCrossRef
40.
Ricoult SJ, Yecies JL, Ben-Sahra I, Manning BD. Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP. Oncogene. 2016;35(10):1250.PubMedCrossRef
41.
Kim J, Guan K-L. mTOR as a central hub of nutrient signalling and cell growth. Nat Cell Biol. 2019;21(1):63.PubMedCrossRef
42.
Hansel DE, Platt E, Orloff M, Harwalker J, Sethu S, Hicks JL, De Marzo A, Steinle RE, Hsi ED, Theodorescu D. Mammalian target of rapamycin (mTOR) regulates cellular proliferation and tumor growth in urothelial carcinoma. Am J Pathol. 2010;176(6):3062–72.PubMedPubMedCentralCrossRef
43.
Knowles MA, Platt FM, Ross RL, Hurst CD. Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer. Cancer Metastasis Rev. 2009;28(3–4):305–16.PubMedPubMedCentralCrossRef
44.
Wang W, Shen T, Dong B, Creighton CJ, Meng Y, Zhou W, Shi Q, Zhou H, Zhang Y, Moore DD. MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling. J Clin Investig. 2019;129(3):1015–29.PubMedCrossRefPubMedCentral
45.
Martin DT, Shen H, Steinbach-Rankins JM, Zhu X, Johnson KK, Syed J, Saltzman WM, Weiss RM. Glycoprotein-130 expression is associated with aggressive bladder cancer and is a potential therapeutic target. Mol Cancer Ther. 2019;18(2):413–20.PubMedCrossRef
46.
47.
Fu G, Xu Z, Chen X, Pan H, Wang Y, Jin B. CDCA5 functions as a tumor promoter in bladder cancer by dysregulating mitochondria-mediated apoptosis, cell cycle regulation and PI3k/AKT/mTOR pathway activation. J Cancer. 2020;11(9):2408.PubMedPubMedCentralCrossRef
48.
Tao T, Su Q, Xu S, Deng J, Zhou S, Zhuang Y, Huang Y, He C, He S, Peng M. Down-regulation of PKM2 decreases FASN expression in bladder cancer cells through AKT/mTOR/SREBP-1c axis. J Cell Physiol. 2019;234(3):3088–104.PubMedCrossRef
49.
Jiang B, Li E-H, Lu Y-Y, Jiang Q, Cui D, Jing Y-F, Xia S-J. Inhibition of fatty-acid synthase suppresses P-AKT and induces apoptosis in bladder cancer. Urology. 2012;80(2):484.e9-484.e15.CrossRef
50.
Su Q, Tao T, Tang L, Deng J, Darko KO, Zhou S, Peng M, He S, Zeng Q, Chen AF. Down-regulation of PKM 2 enhances anticancer efficiency of THP on bladder cancer. J Cell Mol Med. 2018;22(5):2774–90.PubMedPubMedCentralCrossRef
51.
Ikenoue T, Inoki K, Yang Q, Zhou X, Guan KL. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 2008;27(14):1919–31.PubMedPubMedCentralCrossRef
52.
Patel R, Islam S, Bommareddy RR, Smalley T, Acevedo-Duncan M. Simultaneous inhibition of atypical protein kinase-C and mTOR impedes bladder cancer cell progression. Int J Oncol. 2020;56(6):1373–86.PubMedPubMedCentral
53.
Lv X-Y, Ma L, Chen J-F, Yu R, Li Y, Yan ZJ, Cheng Y, Ma Q. Knockdown of DUXAP10 inhibits proliferation and promotes apoptosis in bladder cancer cells via PI3K/Akt/mTOR signaling pathway. Int J Oncol. 2018;52(1):288–94.PubMed
54.
Zhang L, Zhang X, Wang X, He M, Qiao S. MicroRNA-224 promotes tumorigenesis through downregulation of caspase-9 in triple-negative breast cancer. Dis Mark. 2019.
55.
56.
Zhai X, Xu W. Long noncoding RNA ATB promotes proliferation, migration, and invasion in bladder cancer by suppressing microRNA-126. Oncol Res Featur Preclin Clin Cancer Ther. 2018;26(7):1063–72.
57.
Chen L, Long Y, Han Z, Yuan Z, Liu W, Yang F, Li T, Shu L, Zhong Y. MicroRNA-101 inhibits cell migration and invasion in bladder cancer via targeting FZD4. Exp Ther Med. 2019;17(2):1476–85.PubMed
58.
Jiang H, Bu Q, Zeng M, Xia D, Wu A. MicroRNA-93 promotes bladder cancer proliferation and invasion by targeting PEDF. Urol Oncol Semin Orig Investig. 2019;37:150–7.
59.
Scheffer A-R, Holdenrieder S, Kristiansen G, von Ruecker A, Müller SC, Ellinger J. Circulating microRNAs in serum: novel biomarkers for patients with bladder cancer? World J Urol. 2014;32(2):353–8.PubMedCrossRef
60.
Yu Q, Liu P, Li Z, Zhang C, Chen S, Li Z, Zhang G, Li J. MiR-103/107 induces tumorigenicity in bladder cancer cell by suppressing PTEN. Eur Rev Med Pharmacol Sci. 2018;22(24):8616–23.PubMed
61.
Han KS, Jeong IG, Joung JY, Yang SO, Chung J, Seo HK, Kwon KS, Park WS, Lee KH. Clinical value of PTEN in patients with superficial bladder cancer. Urol Int. 2008;80(3):264–9.PubMedCrossRef
62.
63.
Tsai T-F, Lin J-F, Chou K-Y, Lin Y-C, Chen H-E. Hwang TI-S: miR-99a-5p acts as tumor suppressor via targeting to mTOR and enhances RAD001-induced apoptosis in human urinary bladder urothelial carcinoma cells. OncoTargets Therapy. 2018;11:239.PubMedCrossRefPubMedCentral
64.
Kwon JK, Kim SJ, Kim JH, Lee KM, Chang IH. Dual inhibition by S6K1 and Elf4E is essential for controlling cellular growth and invasion in bladder cancer. Urol Oncol Semin Orig Investig. 2014;32:51.e27-51.e35.
65.
Xu C, Zeng Q, Xu W, Jiao L, Chen Y, Zhang Z, Wu C, Jin T, Pan A, Wei R. miRNA-100 inhibits human bladder urothelial carcinogenesis by directly targeting mTOR. Mol Cancer Ther. 2013;12(2):207–19.PubMedCrossRef
66.
Zhuang J, Shen L, Yan J, Guo H. Cancer-associated fibroblasts secreted exosomal miR-146a promotes bladder cancer progression. Eur Urol Suppl. 2017;16(3):e898–9.CrossRef
67.
Tao J, Lu Q, Wu D, Li P, Xu B, Qing W, Wang M, Zhang Z, Zhang W. microRNA-21 modulates cell proliferation and sensitivity to doxorubicin in bladder cancer cells. Oncol Rep. 2011;25(6):1721–9.PubMed
68.
Yang C, Yuan W, Yang X, Li P, Wang J, Han J, Tao J, Li P, Yang H, Lv Q. Circular RNA circ-ITCH inhibits bladder cancer progression by sponging miR-17/miR-224 and regulating p21, PTEN expression. Mol Cancer. 2018;17(1):19.PubMedPubMedCentralCrossRef
69.
Cheng Y, Yang X, Deng X, Zhang X, Li P, Tao J, Lu Q. MicroRNA-218 inhibits bladder cancer cell proliferation, migration, and invasion by targeting BMI-1. Tumor Biol. 2015;36(10):8015–23.CrossRef
70.
Zeng LP, Hu ZM, Li K, Xia K. miR-222 attenuates cisplatin-induced cell death by targeting the PPP 2R2A/Akt/mTOR Axis in bladder cancer cells. J Cell Mol Med. 2016;20(3):559–67.PubMedPubMedCentralCrossRef
71.
Xiao J, Lin H-Y, Zhu Y-Y, Zhu Y-P, Chen L-W. MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the PIK3R2-mediated PI3K/Akt signaling pathway. OncoTargets Therapy. 2016;9:5181.PubMedCrossRefPubMedCentral
72.
Jia A, Castillo-Martin M, Bonal D, Sánchez-Carbayo M, Silva J, Cordon-Cardo C. MicroRNA-126 inhibits invasion in bladder cancer via regulation of ADAM9. Br J Cancer. 2014;110(12):2945.PubMedPubMedCentralCrossRef
73.
Liu S, Chen Q, Wang Y. MiR-125b-5p suppresses the bladder cancer progression via targeting HK2 and suppressing PI3K/AKT pathway. Hum Cell. 2020;33(1):185–94.PubMedCrossRef
74.
Lee H, Jun S-Y, Lee Y-S, Lee HJ, Lee WS, Park CS. Expression of miRNAs and ZEB1 and ZEB2 correlates with histopathological grade in papillary urothelial tumors of the urinary bladder. Virchows Arch. 2014;464(2):213–20.PubMedCrossRef
75.
Zhang HH, Huang ZX, Zhong SQ, Fei KL, Cao YH. miR-21 inhibits autophagy and promotes malignant development in the bladder cancer T24 cell line. Int J Oncol. 2020;56(4):986–98.PubMed
76.
Wang F, Wu H, Fan M, Yu R, Zhang Y, Liu J, Zhou X, Cai Y, Huang S, Hu Z. Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells. FASEB J. 2020;34(3):4266–82.CrossRefPubMed
77.
Wang F, Cao M, Fan M, Wu H, Huang W, Zhang Y, Hu Z, Jin X. AMPK-mTOR-ULK1 axis activation-dependent autophagy promotes hydroxycamptothecin-induced apoptosis in human bladder cancer cells. J Cell Physiol. 2020;235(5):4302–15.PubMedCrossRef
78.
Kratz JM, Grienke U, Scheel O, Mann SA, Rollinger JM. Natural products modulating the hERG channel: heartaches and hope. Nat Product Rep. 2017;34(8):957–80.CrossRef
79.
Kusari S, Pandey SP, Spiteller M. Untapped mutualistic paradigms linking host plant and endophytic fungal production of similar bioactive secondary metabolites. Phytochemistry. 2013;91:81–7.PubMedCrossRef
80.
81.
Biesalski HK. Polyphenols and inflammation: basic interactions. Curr Opin Clin Nutr Metab Care. 2007;10(6):724–8.PubMedCrossRef
82.
Li D, Wang G, Jin G, Yao K, Zhao Z, Bie L, Guo Y, Li N, Deng W, Chen X. Resveratrol suppresses colon cancer growth by targeting the AKT/STAT3 signaling pathway. Int J Mol Med. 2019;43(1):630–40.PubMed
83.
Yang Z, Xie Q, Chen Z, Ni H, Xia L, Zhao Q, Chen Z, Chen P. Resveratrol suppresses the invasion and migration of human gastric cancer cells via inhibition of MALAT1-mediated epithelial-to-mesenchymal transition. Exp Ther Med. 2019;17(3):1569–78.PubMed
84.
Kumar A, Levenson AS. Epigenetic mechanisms of resveratrol and its analogs in cancer prevention and treatment. In: Epigenetics of cancer prevention. Elsevier; 2019. p 169–186.
85.
Khan MA, Chen H-C, Wan X-X, Tania M, Xu A-H, Chen F-Z, Zhang D-Z. Regulatory effects of resveratrol on antioxidant enzymes: a mechanism of growth inhibition and apoptosis induction in cancer cells. Mol Cells. 2013;35(3):219–25.PubMedPubMedCentralCrossRef
86.
87.
Rodríguez-Enríquez S, Pacheco-Velázquez SC, Marín-Hernández Á, Gallardo-Pérez JC, Robledo-Cadena DX, Hernández-Reséndiz I, García-García JD, Belmont-Díaz J, López-Marure R, Hernández-Esquivel L. Resveratrol inhibits cancer cell proliferation by impairing oxidative phosphorylation and inducing oxidative stress. Toxicol Appl Pharmacol. 2019. https://​doi.​org/​10.​1016/​j.​taap.​2019.​03.​008.CrossRefPubMed
88.
Bai Y, Mao QQ, Qin J, Zheng XY, Wang YB, Yang K, Shen HF, Xie LP. Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo. Cancer Sci. 2010;101(2):488–93.PubMedCrossRef
89.
Stocco B, Toledo K, Salvador M, Paulo M, Koyama N, Toloi MRT. Dose-dependent effect of resveratrol on bladder cancer cells: chemoprevention and oxidative stress. Maturitas. 2012;72(1):72–8.PubMedCrossRef
90.
Wu M-L, Li H, Yu L-J, Chen X-Y, Kong Q-Y, Song X, Shu X-H, Liu J. Short-term resveratrol exposure causes in vitro and in vivo growth inhibition and apoptosis of bladder cancer cells. PLoS ONE. 2014;9(2):e89806.PubMedPubMedCentralCrossRef
91.
Lin X, Wu G, Huo WQ, Zhang Y, Jin FS. Resveratrol induces apoptosis associated with mitochondrial dysfunction in bladder carcinoma cells. Int J Urol. 2012;19(8):757–64.PubMedCrossRef
92.
Yang Y, Li C, Li H, Wu M, Ren C, Zhen Y, Ma X, Diao Y, Ma X, Deng S. Differential sensitivities of bladder cancer cell lines to resveratol are unrelated to its metabolic profile. Oncotarget. 2017;8(25):40289.PubMedPubMedCentralCrossRef
93.
Alayev A, Salamon RS, Schwartz NS, Berman AY, Wiener SL, Holz MK. Combination of rapamycin and resveratrol for treatment of bladder cancer. J Cell Physiol. 2017;232(2):436–46.PubMedCrossRef
94.
El-Readi MZ, Eid S, Abdelghany AA, Al-Amoudi HS, Efferth T, Wink M. Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2019;55:269–81.PubMedCrossRef
95.
Díaz-Chávez J, Fonseca-Sánchez MA, Arechaga-Ocampo E, Flores-Pérez A, Palacios-Rodríguez Y, Domínguez-Gómez G, Marchat LA, Fuentes-Mera L, Mendoza-Hernández G, Gariglio P. Proteomic profiling reveals that resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy. PLoS ONE. 2013;8(5):e64378.PubMedPubMedCentralCrossRef
96.
97.
Mohammed S, Harikumar KB. Role of resveratrol in chemosensitization of cancer. In: Role of nutraceuticals in cancer chemosensitization. Elsevier; 2018. p 61–76.
98.
Huang F, Wu X-N, Chen J, Wang W-X, Lu ZF. Resveratrol reverses multidrug resistance in human breast cancer doxorubicin-resistant cells. Exp Ther Med. 2014;7(6):1611–6.PubMedPubMedCentralCrossRef
99.
Guo Y, Zhang H, Xie D, Hu X, Song R, Zhu L. Non-coding RNA NEAT1/miR-214-3p contribute to doxorubicin resistance of urothelial bladder cancer preliminary through the Wnt/β-catenin pathway. Cancer Manag Res. 2018;10:4371.PubMedPubMedCentralCrossRef
100.
Mao QQ, Bai Y, Lin YW, Zheng XY, Qin J, Yang K, Xie LP. Resveratrol confers resistance against taxol via induction of cell cycle arrest in human cancer cell lines. Mol Nutr Food Res. 2010;54(11):1574–84.PubMedCrossRef
101.
Wang S, Meng Q, Xie Q, Zhang M. Effect and mechanism of resveratrol on drug resistance in human bladder cancer cells. Mol Med Rep. 2017;15(3):1179–87.PubMedPubMedCentralCrossRef
102.
Almeida TC, Guerra CCC, De Assis BLG, de Soares RD, Garcia CCM, Lima AA, da Silva GN. Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status. Environ Mol Mutag. 2019;60(8):740–51.CrossRef
103.
Zhou C, Ding J, Wu Y. Resveratrol induces apoptosis of bladder cancer cells via miR-21 regulation of the Akt/Bcl-2 signaling pathway. Mol Med Rep. 2014;9(4):1467–73.PubMedCrossRef
104.
Hong L, Han Y, Zhang Y, Zhang H, Zhao Q, Wu K, Fan D. MicroRNA-21: a therapeutic target for reversing drug resistance in cancer. Exp Opin Ther Targets. 2013;17(9):1073–80.CrossRef
105.
Li L, Chen D, Zhu J, Ouyang J, Song B, Shenglong Z, KaiShun L, Wei L, Yun L. Inhibition of resveratrol on bladder cancer and its molecular mechanism. Acta Medica Mediterranea. 2019;35(2):797–802.
106.
Jing X, Cheng W, Wang S, Li P, He L. Resveratrol induces cell cycle arrest in human gastric cancer MGC803 cells via the PTEN-regulated PI3K/Akt signaling pathway. Oncol Rep. 2016;35(1):472–8.PubMedCrossRef
107.
Zheng M, Chen R, Zhong H, Lin Q, Wang X, Zhao Z, Xie L. Side-effects of resveratrol in HepG2 cells: reduced pten and increased bcl-xl mRNA expression. Mol Med Rep. 2012;6(6):1367–70.PubMedCrossRef
108.
Dhar S, Kumar A, Rimando AM, Zhang X, Levenson AS. Resveratrol and pterostilbene epigenetically restore PTEN expression by targeting oncomiRs of the miR-17 family in prostate cancer. Oncotarget. 2015;6(29):27214.PubMedPubMedCentralCrossRef
109.
Kumar A, Rimando AM, Levenson AS. Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer. Ann N Y Acad Sci. 2017;1403(1):15–26.PubMedCrossRef
110.
Davidov-Pardo G, McClements DJ. Resveratrol encapsulation: designing delivery systems to overcome solubility, stability and bioavailability issues. Trends Food Sci Technol. 2014;38(2):88–103.CrossRef
111.
Venditti I, Iucci G, Fratoddi I, Cipolletti M, Montalesi E, Marino M, Secchi V, Battocchio C. Direct conjugation of resveratrol on hydrophilic gold nanoparticles: structural and cytotoxic studies for biomedical applications. Nanomaterials. 2020;10(10):1898.PubMedCentralCrossRef
112.
Chamsai B, Samprasit W, Opanasopit P, Benjasirimongkol P, Sriamornsak P. Types of solid lipids on physical stability of resveratrol-loaded nanostructured lipid carriers. Key Eng Mater. 2020;859:203–7.CrossRef
113.
114.
Mirzaei H, Masoudifar A, Sahebkar A, Zare N, Sadri Nahand J, Rashidi B, Mehrabian E, Mohammadi M, Mirzaei HR, Jaafari MR. MicroRNA: a novel target of curcumin in cancer therapy. J Cell Physiol. 2018;233(4):3004–15.PubMedCrossRef
115.
Sun M, Estrov Z, Ji Y, Coombes KR, Harris DH, Kurzrock R. Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther. 2008;7(3):464–73.PubMedCrossRef
116.
Hatab HM, Hamid FFA, Soliman AF, Al-Shafie TA, Ismail YM, El-Houseini ME. A combined treatment of curcumin, piperine, and taurine alters the circulating levels of IL-10 and miR-21 in hepatocellular carcinoma patients: a pilot study. J Gastrointest Oncol. 2019;10(4):766.PubMedPubMedCentralCrossRef
117.
Lelli D, Pedone C, Sahebkar A. Curcumin and treatment of melanoma: the potential role of microRNAs. Biomed Pharmacother. 2017;88:832–4.PubMedCrossRef
118.
Xu R, Li H, Wu S, Qu J, Yuan H, Zhou Y, Lu Q. MicroRNA-1246 regulates the radio-sensitizing effect of curcumin in bladder cancer cells via activating P53. Int Urol Nephrol. 2019;51(10):1771–9.PubMedCrossRef
119.
Saini S, Arora S, Majid S, Shahryari V, Chen Y, Deng G, Yamamura S, Ueno K, Dahiya R. Curcumin modulates MicroRNA-203-mediated regulation of the Src-Akt axis in bladder cancer. Cancer Prev Res. 2011;4(10):1698–709.CrossRef
120.
Wang K, Tan S-L, Lu Q, Xu R, Cao J, Wu S-Q, Wang Y-H, Zhao X-K, Zhong Z-H. Curcumin suppresses microRNA-7641-mediated regulation of p16 expression in bladder cancer. Am J Chin Med. 2018;46(06):1357–68.PubMedCrossRef
121.
Network CGAR. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315–22.CrossRef
122.
Liu ST, Hui G, Mathis C, Chamie K, Pantuck AJ, Drakaki A. The current status and future role of the phosphoinositide 3 kinase/AKT signaling pathway in urothelial cancer: an old pathway in the new immunotherapy era. Clin Genitourinary Cancer. 2018;16(2):e269–76.CrossRef
123.
Winters BR, Vakar-Lopez F, Brown L, Montgomery B, Seiler R, Black PC, Boormans JL, Dall M, Davincioni E, Douglas J. Mechanistic target of rapamycin (MTOR) protein expression in the tumor and its microenvironment correlates with more aggressive pathology at cystectomy. Urol Oncol Semin Orig Investig. 2018;36:342.e7-e314.e14.
124.
Liu J, Zeng Q, Cao P, Xie D, Yang F, He L, Dai Y, Li J, Liu X, Zeng H. SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival. Oncogene. 2018b;37(29):3937–52.CrossRefPubMed
125.
Tian B, Zhao Y, Liang T, Ye X, Li Z, Yan D, Fu Q, Li Y. Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. J Drug Target. 2017;25(7):626–36.PubMedCrossRef
126.
Wang J, Wang Z, Wang H, Zhao J, Zhang Z. Curcumin induces apoptosis in ej bladder cancer cells via modulating c-myc and pi3k/akt signaling pathway. World J Oncol. 2011;2(3):113.PubMedPubMedCentral
127.
128.
El-Shafey AA, Hegab MH, Seliem MM, Barakat AM, Mostafa NE, Abdel-Maksoud HA, Abdelhameed RM. Curcumin@ metal organic frameworks nano-composite for treatment of chronic toxoplasmosis. J Mater Sci Mater Med. 2020;31(11):1–13.CrossRef
129.
130.
Wei Y, Pu X, Zhao L. Preclinical studies for the combination of paclitaxel and curcumin in cancer therapy. Oncol Rep. 2017;37(6):3159–66.PubMedCrossRef
131.
Zhao Y-f, Han M-l, Xiong Y-j, Wang L, Fei Y, Shen X, Zhu Y, Liang Z-q. A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial–mesenchymal transition. Acta Pharmacol Sinica. 2018;39(6):1034–47.CrossRef
132.
Lu C, Xie Z, Peng Q. MiRNA-107 enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bcl-w in non small cell lung cancer. Am J Cancer Res. 2017;7(9):1863.PubMedPubMedCentral
133.
Wang S-Q, Wang C, Chang L-M, Zhou K-R, Wang J-W, Ke Y, Yang D-X, Shi H-G, Wang R, Shi X-L. Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway. Oncotarget. 2016;7(45):72990.PubMedPubMedCentralCrossRef
134.
Papadopoulos EI, Scorilas A. Cisplatin and paclitaxel alter the expression pattern of miR-143/145 and miR-183/96/182 clusters in T24 bladder cancer cells. Clin Transl Sci. 2015;8(6):668–75.PubMedPubMedCentralCrossRef
135.
Kunnumakkara AB, Harsha C, Banik K, Vikkurthi R, Sailo BL, Bordoloi D, Gupta SC, Aggarwal BB. Is curcumin bioavailability a problem in humans: lessons from clinical trials. Exp Opin Drug Metab Toxicol. 2019;15(9):705–33.CrossRef
136.
Hsieh C. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(2895):e2900.
137.
Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Prev Biomark. 2005;14(1):120–5.
138.
Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004;10(20):6847–54.PubMedCrossRef
139.
Durgaprasad S, Pai CG, Alvres JF. A pilot study of the antioxidant effect of curcumin in tropical pancreatitis. Indian J Med Res. 2005;122(4):315.PubMed
140.
Roth BJ. Preliminary experience with paclitaxel in advanced bladder cancer. Semin Oncol. 1995;22:1–5.PubMed
141.
Albers P, Park S-I, Niegisch G, Fechner G, Steiner U, Lehmann J, Heimbach D, Heidenreich A, Fimmers R, Siener R. Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]. Ann Oncol. 2011;22(2):288–94.PubMedCrossRef
142.
Paz-Ares L, Solsona E, Esteban E, Saez A, Gonzalez-Larriba J, Anton A, Hevia M, de la Rosa F, Guillem V, Bellmunt J. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. J Clin Oncol. 2010;28(18):518–518.
143.
Sridhar SS, Blais N, Tran B, Reaume MN, North SA, Stockler MR, Chi KN, Fleshner NE, Liu G, Robinson JW. Efficacy and Safety of nab-Paclitaxel vs paclitaxel on survival in patients with Platinum-refractory metastatic urothelial cancer: the Canadian Cancer Trials Group BL. 12 Randomized Clinical Trial. JAMA Oncol. 2020;6:1–8.CrossRefPubMedCentral
144.
Singh AP, Singh R, Verma SS, Rai V, Kaschula CH, Maiti P, Gupta SC. Health benefits of resveratrol: evidence from clinical studies. Med Res Rev. 2019;39(5):1851–91.PubMedCrossRef
145.
Howells LM, Berry DP, Elliott PJ, Jacobson EW, Hoffmann E, Hegarty B, Brown K, Steward W, Gescher AJ. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases—safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res. 2011;4(9):1419–25.CrossRef
146.
Patel KR, Brown VA, Jones DJ, Britton RG, Hemingway D, Miller AS, West KP, Booth TD, Perloff M, Crowell JA. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res. 2010;70(19):7392–9.PubMedPubMedCentralCrossRef
147.
Kjær TN, Ornstrup MJ, Poulsen MM, Jørgensen JOL, Hougaard DM, Cohen AS, Neghabat S, Richelsen B, Pedersen SB. Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men. Prostate. 2015;75(12):1255–63.PubMedCrossRef
148.
Paller CJ, Rudek MA, Zhou XC, Wagner WD, Hudson TS, Anders N, Hammers HJ, Dowling D, King S, Antonarakis ES. A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: safety, tolerability, and dose determination. Prostate. 2015;75(14):1518–25.PubMedPubMedCentralCrossRef
149.
Popat R, Plesner T, Davies F, Cook G, Cook M, Elliott P, Jacobson E, Gumbleton T, Oakervee H, Cavenagh J. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol. 2012;160(5):714–7.PubMedCrossRef
150.
Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, Ng CS, Badmaev V, Kurzrock R. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14(14):4491–9.PubMedCrossRef
Metadata
Title
Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer
Authors
Khushbukhat Khan
Cristina Quispe
Zeeshan Javed
Muhammad Javed Iqbal
Haleema Sadia
Shahid Raza
Asma Irshad
Bahare Salehi
Željko Reiner
Javad Sharifi-Rad
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Biomarkers
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01660-7

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