DOI QR코드

DOI QR Code

Resveratrol Affects Protein Kinase C Activity and Promotes Apoptosis in Human Colon Carcinoma Cells

  • Fang, Jie-Yu (Department of Anesthesia, Sun Yat-sen University) ;
  • Li, Zhi-Hua (Department of Gynecology&Obstetrics, The Third Affiliated Hospital, Guangzhou Medical College) ;
  • Li, Qiang (Department of Surgery, The First Affiliated Hospital, Sun Yat-sen University) ;
  • Huang, Wen-Sheng (Department of Surgery, The First Affiliated Hospital, Sun Yat-sen University) ;
  • Kang, Liang (Department of Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University) ;
  • Wang, Jian-Ping (Department of Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University)
  • Published : 2012.12.31

Abstract

Background: Resveratrol has been reported to have potential chemopreventive and apoptosis-inducing properties in a variety of tumor cell lines. Objective: In this study, to investigate the effects of resveratrol on protein kinase C (PKC) activity and apoptosis in human colon carcinoma cells, we used HT-29 cells and examined the $PKC{\alpha}$ and ERK1/2 signaling pathways. Methods: To test the effects of resveratrol on the growth of HT-29 cells, the cells were exposed to varying concentrations and assessed with the the MTT cell-viability assay. Fluorescence-activated cell sorter (FACS) analysis was applieded to determine the effects of resveratrol on cell apoptosis. Western blotting was performed to determine the protein levels of $PKC{\alpha}$ and ERK1/2. In inhibition experiments, HT-29 cells were treated with G$\ddot{o}$6976 or PD98059 for 30 min, followed by exposure to $200{\mu}M$ resveratrol for 72 h. Results: Resveratrol had a significant inhibitory effect on HT-29 cell growth. FACS revealed that resveratrol induced apoptosis. Western blotting showed that e phosphorylation of $PKC{\alpha}$ and ERK1/2 was significantly increased in response to resveratrol treatment. Pre-treatment with $PKC{\alpha}$ and ERK1/2 inhibitors (G$\ddot{o}$6976 and PD98059) promoted apoptosis. Conclusion: Resveratrol has significant anti-proliferative effects on the colon cancer cell line HT-29. The PKC-ERK1/2 signaling pathway can partially mediate resveratrol-induced apoptosis of HT-29 cells.

Keywords

Resveratrol;HT;29 cells;apoptosis;PKC;ERK1/2 signaling pathway

References

  1. Wu GS (2007). Role of mitogen-activated protein kinase phosphatases (MKPs) in cancer. Cancer Metastasis Rev, 26, 579-85. https://doi.org/10.1007/s10555-007-9079-6
  2. Yang CS, Landau JM, Huang MT, et al (2001). Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr, 21, 381-406. https://doi.org/10.1146/annurev.nutr.21.1.381
  3. Kirkegaard H, Johnsen NF, Christensen J, et al (2010). Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study. BMJ, 341, 5504. https://doi.org/10.1136/bmj.c5504
  4. Komatsu K, Buchanan FG, Otaka M, et al (2006). Gene expression profiling following constitutive activation of MEK1 and transformation of rat intestinal epithelial cells. Mol Cancer, 5, 63. https://doi.org/10.1186/1476-4598-5-63
  5. Ling LU, Lin H, Tan KB, et al (2009). The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells. Int J Oncol, 35, 1463-71.
  6. Lynch HT, Lynch JF (1998). Genetics of colonic cancer. Digestion, 59, 481-92. https://doi.org/10.1159/000007525
  7. Marel AK, Lizard G, Izard JC, et al (2008). Inhibitory effects of trans-resveratrol analogs molecules on the proliferation and the cell cycle progression of human colon tumoral cells. Mol Nutr Food Res, 52, 538-48. https://doi.org/10.1002/mnfr.200700185
  8. McCubrey JA, Steelman LS, Chappell WH, et al (2007). Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta, 1773, 1263-84. https://doi.org/10.1016/j.bbamcr.2006.10.001
  9. McMillan L, Butcher SK, Pongracz J, et al (2003). Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases. Br J Cancer, 88, 748-53. https://doi.org/10.1038/sj.bjc.6600793
  10. MurrayNR, Kalari KR, Fields AP (2011). Protein kinase Ciota expression and oncogenic signaling mechanisms in cancer. J Cell Physiol, 226, 879-87. https://doi.org/10.1002/jcp.22463
  11. Peyssonnaux C, Eychene A (2001). Eychene, The Raf/MEK/ ERK pathway: new concepts of activation. Biol Cell, 93, 53-62. https://doi.org/10.1016/S0248-4900(01)01125-X
  12. Schutze M, Boeing H, Pischon T, et al (2011). Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study. BMJ, 342, 1584. https://doi.org/10.1136/bmj.d1584
  13. Shih A, Zhang S, Cao HJ, et al (2004). Inhibitory effect of epidermal growth factor on resveratrol-induced apoptosis in prostate cancer cells is mediated by protein kinase C-alpha. Mol Cancer Ther, 3, 1355-64.
  14. Telang NT, Li G, Katdare M (2006). Prevention of earlyonset familial/hereditary colon cancer: new models and mechanistic biomarkers. Int J Oncol, 28, 1523-9.
  15. Tian F, Wu H, Li Z, et al (2009). Activated PKCalpha/ERK1/2 signaling inhibits tamoxifen-induced apoptosis in C6 cells. Cancer Invest, 27, 802-8. https://doi.org/10.1080/07357900802672720
  16. Wang TT, Schoene NW, Kim YS, et al (2010). Differential effects of resveratrol and its naturally occurring methylether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells. Mol Nutr Food Res, 54, 335-44. https://doi.org/10.1002/mnfr.200900143
  17. Wen-Sheng W (2006). Protein kinase C alpha trigger Ras and Raf-independent MEK/ERK activation for TPA-induced growth inhibition of human hepatoma cell HepG2. Cancer Lett, 239, 27-35. https://doi.org/10.1016/j.canlet.2005.07.034
  18. Wolter F, Ulrich S, Stein J (2004). Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer: key role of polyamines? J Nutr, 134, 3219-22.
  19. Brackmann S, Andersen SN, Aamodt G, et al (2009). Relationship between clinical parameters and the colitiscolorectal cancer interval in a cohort of patients with colorectal cancer in inflammatory bowel disease. Scand J Gastroenterol, 44, 46-55. https://doi.org/10.1080/00365520801977568
  20. Carter CA (2000). Protein kinase C as a drug target: implications for drug or diet prevention and treatment of cancer. Curr Drug Targets, 1, 163-83. https://doi.org/10.2174/1389450003349317
  21. Davies CC, Chakraborty A, Cipriani F, et al (2010). Identification of a co-activator that links growth factor signalling to c-Jun/ AP-1 activation. Nat Cell Biol, 12, 963-72. https://doi.org/10.1038/ncb2098
  22. De Silva WI (1992). Relationships of desire for no more children and socioeconomic and demographic factors in Sri Lankan women. J Biosoc Sci, 24, 185-99.
  23. Edwards BK, Ward E, Kohler BA, et al (2010). Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer, 116, 544-73. https://doi.org/10.1002/cncr.24760
  24. Endo H, Hosono K, Fujisawa T, et al (2009). Involvement of JNK pathway in the promotion of the early stage of colorectal carcinogenesis under high-fat dietary conditions. Gut, 58, 1637-43. https://doi.org/10.1136/gut.2009.183624
  25. Filomeni G, Graziani I, Rotilio G, et al (2007). Trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways. Genes Nutr, 2, 295-305. https://doi.org/10.1007/s12263-007-0059-9
  26. Fukui M, Yamabe N, Zhu BT(2010). Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo. Eur J Cancer, 46, 1882-91. https://doi.org/10.1016/j.ejca.2010.02.004
  27. Hope C, Planutis K, Planutiene M, et al (2008). Low concentrations of resveratrol inhibit Wnt signal throughput in colon-derived cells: implications for colon cancer prevention. Mol Nutr Food Res, 52, S52-61.
  28. Hsieh TC, Huang YC, Wu JM(2011). Control of prostate cell growth, DNA damage and repair and gene expression by resveratrol analogues, in vitro. Carcinogenesis, 32, 93-101. https://doi.org/10.1093/carcin/bgq230
  29. Jang M, Cai L, Udeani GO, et al (1997). Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 275, 218-20. https://doi.org/10.1126/science.275.5297.218
  30. Juan ME, Wenzel U, Daniel H, et al (2008). Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells. J Agric Food Chem, 56, 4813-8. https://doi.org/10.1021/jf800175a
  31. Kambara T, Simms LA, Whitehall VL, et al (2004). BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut, 53, 1137-44. https://doi.org/10.1136/gut.2003.037671
  32. Keller JW, Franklin JL, Graves-Deal R, et al (2007). Oncogenic KRAS provides a uniquely powerful and variable oncogenic contribution among RAS family members in the colonic epithelium. J Cell Physiol, 2103, 740-9.
  33. Kim MJ, Park IJ, Yun H, et al (2010). AMP-activated protein kinase antagonizes pro-apoptotic extracellular signalregulated kinase activation by inducing dual-specificity protein phosphatases in response to glucose deprivation in HCT116 carcinoma. J Biol Chem, 285, 14617-27. https://doi.org/10.1074/jbc.M109.085456
  34. Abrams SL, Steelman LS, Shelton JG, et al (2010). The Raf/ MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy. Cell Cycle, 9, 1781-91. https://doi.org/10.4161/cc.9.9.11483
  35. Atten MJ, Godoy-Romero E, Attar BM, et al (2005). Resveratrol regulates cellular PKC alpha and delta to inhibit growth and induce apoptosis in gastric cancer cells. Invest New Drugs, 23, 111-9. https://doi.org/10.1007/s10637-005-5855-8

Cited by

  1. Targeting Cancer with Nano-Bullets: Curcumin, EGCG, Resveratrol and Quercetin on Flying Carpets vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3865
  2. The PTEN/PI3K/Akt and Wnt/β-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation vol.45, pp.1, 2014, https://doi.org/10.3892/ijo.2014.2392
  3. Time - and Concentration - Dependent Effects of Resveratrol on miR 15a and miR16-1 Expression and Apoptosis in the CCRF-CEM Acute Lymphoblastic Leukemia Cell Line vol.16, pp.15, 2015, https://doi.org/10.7314/APJCP.2015.16.15.6463