RESVERATROL INHIBITS EXPRESSION OF CANCER-SPECIFIC PENTOSE PHOSPHATE PATHWAY ENZYME TKTL1
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i6.25021Keywords:
Resveratrol, Transketolase-like 1, HeLa, Pentose phosphate pathwayAbstract
Objective: The objective of this study was to identify cancer-specific metabolic enzyme Transketolase-like 1 (TKTL1) from pentose phosphate pathway as target of resveratrol, a naturally occurring nutraceutical.
Methods: Methylthiazolyldiphenyl-tetrazolium bromide assay and trypan blue assay were used for the estimation of growth and proliferation. Reactive oxygen species (ROS) was estimated using 2'-7'-Dichlorodihydrofluorescein diacetate while reduced glutathione (GSH) was estimated using commercially available kit. Promoter activity, reverse transcription polymerase chain reaction, and western blotting were used for expression analysis.
Results: Resveratrol treatment in HeLa cells inhibited proliferation, promoted ROS, and reduced intracellular GSH levels. In TKTL1 promoter activity assay, we found that resveratrol treatment directly inhibited promoter activity of TKTL1. Resveratrol inhibited both mRNA and protein expression of TKTL1 in a dose-dependent manner.
Conclusion: This is the first report where we show that resveratrol inhibits cancer-specific isoform TKTL1 as one of its targets to elicit its anticancer activity.
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Sun W, Liu Y, Glazer CA, Shao C, Bhan S, Demokan S, et al. TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1alpha stabilization. Clin Cancer Res 2010;16:857-66.
Dong Y, Wang M. Knockdown of TKTL1 additively complements cisplatin-induced cytotoxicity in nasopharyngeal carcinoma cells by regulating the levels of NADPH and ribose-5-phosphate. Biomed Pharmacother 2017;85:672-8.
Li J, Zhu SC, Li SG, Zhao Y, Xu JR, Song CY, et al. TKTL1 promotes cell proliferation and metastasis in esophageal squamous cell carcinoma. Biomed Pharmacother 2015;74:71-6.
Hu LH, Yang JH, Zhang DT, Zhang S, Wang L, Cai PC, et al. The TKTL1 gene influences total transketolase activity and cell proliferation in human colon cancer loVo cells. Anticancer Drugs 2007;18:427-33.
Langbein S, Zerilli M, Zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, et al. Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br J Cancer 2006;94:578-85.
Song Y, Liu D, He G. TKTL1 and p63 are biomarkers for the poor prognosis of gastric cancer patients. Cancer Biomark 2015;15:591-7.
Grimm M, Munz A, Teriete P, Nadtotschi T, Reinert S. GLUT-1(+)/TKTL1(+) coexpression predicts poor outcome in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:743 53.
Zhang S, Yang JH, Guo CK, Cai PC. Gene silencing of TKTL1 by RNAi inhibits cell proliferation in human hepatoma cells. Cancer Lett 2007;253:108-14.
Yuan W, Wu S, Guo J, Chen Z, Ge J, Yang P, et al. Silencing of TKTL1 by siRNA inhibits proliferation of human gastric cancer cells in vitro and in vivo. Cancer Biol Ther 2010;9:710-6.
Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275:218-20.
Mohamed H. Anti-obesity effect of resveratrol in rats on high fat diet through regulation of gene expression of visceral white adipose tissue. Int J Pharm Pharm Sci 2016;8:378-384.
Lalitha V, Korah MC, Sengottuvel S, Sivakumar T. Antidiabetic and antioxidant activity of resveratrol and vitamin-c combination on streptozotocin induced diabetic rats. Int J Pharm Pharm Sci 2015;7:455 8.
Lin JN, Lin VC, Rau KM, Shieh PC, Kuo DH, Shieh JC, et al. Resveratrol modulates tumor cell proliferation and protein translation via SIRT1-dependent AMPK activation. J Agric Food Chem 2010;58:1584-92.
Quoc Trung L, Espinoza JL, Takami A, Nakao S. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition. PLoS One 2013;8:e55183.
Iqbal MA, Bamezai RN. Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin. PLoS One 2012;7:e36764.
Kumar B, Iqbal MA, Singh RK, Bamezai RN. Resveratrol inhibits TIGAR to promote ROS induced apoptosis and autophagy. Biochimie 2015;118:26-35.
Gomez LS, Zancan P, Marcondes MC, Ramos-Santos L, Meyer-Fernandes JR, Sola-Penna M, et al. Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase. Biochimie 2013;95:1336-43.
Kumar B, Bamezai RN. Moderate DNA damage promotes metabolic flux into PPP via PKM2 Y-105 phosphorylation: A feature that favours cancer cells. Mol Biol Rep 2015;42:1317-21.
Diaz-Moralli S, Aguilar E, Marin S, Coy JF, Dewerchin M, Antoniewicz MR, et al. A key role for transketolase-like 1 in tumor metabolic reprogramming. Oncotarget 2016;7:51875-97.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the warburg effect: The metabolic requirements of cell proliferation. Science 2009;324:1029-33.
Jiang P, Du W, Wu M. Regulation of the pentose phosphate pathway in cancer. Protein Cell 2014;5:592-602.
Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxid Redox Signal 2008;10:1343-74.
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