DOI QR코드

DOI QR Code

Pristimerin, a Naturally Occurring Triterpenoid, Exerts Potent Anticancer Effect in Colon Cancer Cells

  • Seo, Hee Won (Department of Biomedical Science, Catholic University of Daegu) ;
  • Park, Ju-Hyung (Department of Biomedical Science, Catholic University of Daegu) ;
  • Lee, Ji Yeon (Department of Biomedical Science, Catholic University of Daegu) ;
  • Park, Hyun-Ju (Department of Biomedical Science, Catholic University of Daegu) ;
  • Kim, Jin-Kyung (Department of Biomedical Science, Catholic University of Daegu)
  • 투고 : 2018.01.26
  • 심사 : 2018.02.23
  • 발행 : 2018.03.31

초록

Pristimerin is a triterpene compound isolated from plant extracts that reportedly possesses antitumor, antioxidant, and anti-inflammatory activities. The current study was designed to evaluate the antitumor effects of pristimerin on human colon cancer cells. Treatment of the human colon cancer cells, HCT116 and SW480, with pristimerin led to a dose-dependent decrease in cell proliferation. Flow cytometry experiments showed that pristimerin increased cell apoptotic rate and decreased the mitochondrial membrane potential in HCT116 and SW480 cells. Western blot assay showed that pristimerin induced increased cleavage of caspase-3, -7, -8, and poly ADP ribose polymerase. Treatment with pristimerin also caused a marked decrease in the expression of Bcl-2 and Bcl-xL. Additionally, the levels of phosphorylated AKT and forkhead box O3a (FOXO3a) were decreased in pristimerin-treated colon cancer cells. Taken together, our study illustrated that pristimerin promoted apoptosis via the AKT/FOXO3a signaling pathway in colon cancer cells, elucidating that it might be considered as a potential agent for colon cancer therapy.

키워드

참고문헌

  1. Bo H, van den Heuvel APJ, Varun VP, Shengliang Z, Wafik SED. Targeting tumor suppressor p53 for cancer therapy: Strategies, challenges and opportunities. Current Drug Targets. 2014. 15: 80-89. https://doi.org/10.2174/1389450114666140106101412
  2. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014. 383: 1490-1502. https://doi.org/10.1016/S0140-6736(13)61649-9
  3. Carvalho PR, Silva DH, Bolzani VS, Furlan M. Antioxidant quinonemethide triterpenes from Salacia campestris. Chemistry & Biodiversity. 2005. 2: 367-372. https://doi.org/10.1002/cbdv.200590016
  4. Chen J. The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harbor Perspectives in Medicine. 2016. 6: a026104. https://doi.org/10.1101/cshperspect.a026104
  5. Decker P, Muller S. Modulating poly (ADP-ribose) polymerase activity: potential for the prevention and therapy of pathogenic situations involving DNA damage and oxidative stress. Current Pharmaceutical Biotechnology. 2002. 3: 275-283. https://doi.org/10.2174/1389201023378265
  6. Deeb D, Gao X, Liu YB, Pindolia K, Gautam SC. Pristimerin, a quinonemethide triterpenoid, induces apoptosis in pancreatic cancer cells through the inhibition of pro-survival Akt/$NF-{\kappa}B$/ mTOR signaling proteins and anti-apoptotic Bcl-2. International Journal of Oncology. 2014. 44: 1707-1715. https://doi.org/10.3892/ijo.2014.2325
  7. el-Deiry WS. Regulation of p53 downstream genes. Seminars in Cancer Biology. 1998. 8: 345-57. https://doi.org/10.1006/scbi.1998.0097
  8. Elmore S. Apoptosis: a review of programmed cell death. Toxicologic Pathology. 2007. 35: 495-516. https://doi.org/10.1080/01926230701320337
  9. Fernandez de Mattos S, Villalonga P, Clardy J, Lam EW. FOXO3a mediates the cytotoxic effects of cisplatin in colon cancer cells. Molecular Cancer Therapeutics. 2008. 7: 3237-3246. https://doi.org/10.1158/1535-7163.MCT-08-0398
  10. Gullo FP, Sardi JC, Santos VA, Sangalli-Leite F, Pitangui NS, Rossi SA, de Paula E, Silva AC, Soares LA, Silva JF, Oliveira HC, Furlan M, Silva DH, Bolzani VS, Mendes-Giannini MJ, Fusco-Almeida AM. Antifungal activity of maytenin and pristimerin. Evidence-Based Complementary and Alternative Medicine. 2012. 2012: 340787.
  11. Iacopetta B. TP53 mutation in colorectal cancer. Human Mutation. 2003. 21: 271-276. https://doi.org/10.1002/humu.10175
  12. Kale J, Osterlund EJ, Andrews DW. BCL-2 family proteins: changing partners in the dance towards death. Cell Death & Differentiation. 2018. 25: 65-80. https://doi.org/10.1038/cdd.2017.186
  13. Kim HJ, Park GM, Kim JK. Anti-inflammatory effect of pristimerin on lipopolysaccharide-induced inflammatory responses in murine macrophages. Archives of Pharmacal Research. 2013. 36: 495-500. https://doi.org/10.1007/s12272-013-0054-1
  14. Lee KW, Bode AM, Dong Z. Molecular targets of phytochemicals for cancer prevention. Nature Reviews Cancer. 2011. 11: 211-218. https://doi.org/10.1038/nrc3017
  15. Link W, Fernandez-Marcos PJ. FOXO transcription factors at the interface of metabolism and cancer. International Journal of Cancer. 2017. 141: 2379-2391. https://doi.org/10.1002/ijc.30840
  16. Lopez MR, de Leon L, Moujir L. Antibacterial properties of phenolic triterpenoids against Staphylococcus epidermidis. Planta Medica. 2011. 77: 726-729. https://doi.org/10.1055/s-0030-1250500
  17. Manning BD, Toker A. AKT/PKB Signaling: Navigating the network. Cell. 2017. 169: 381-405. https://doi.org/10.1016/j.cell.2017.04.001
  18. Marsden VS1, O'Connor L, O'Reilly LA, Silke J, Metcalf D, Ekert PG, Huang DC, Cecconi F, Kuida K, Tomaselli KJ, Roy S, Nicholson DW, Vaux DL, Bouillet P, Adams JM, Strasser A. Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature. 2002. 419: 634-637. https://doi.org/10.1038/nature01101
  19. Muller PAJ, Vousden KH. P53 mutations in cancer. Nature Cell Biology. 2013. 15: 2-8. https://doi.org/10.1038/ncb2641
  20. Nagai H, Kim YH. Cancer prevention from the perspective of global cancer burden patterns. Journal of Thoracic Disease. 2017. 9: 448-451. https://doi.org/10.21037/jtd.2017.02.75
  21. Sakai T, Liu L, Teng X, Mukai-Sakai R, Shimada H, Kaji R, Mitani T, Matsumoto M, Toida K, Ishimura K, Shishido Y, Mak TW, Fukui K. Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis. Journal of Biological Chemistry. 2004. 279: 41131-41140. https://doi.org/10.1074/jbc.M402902200
  22. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: A Cancer Journal for Clinicians. 2016. 66: 7-30. https://doi.org/10.3322/caac.21332
  23. Shakeri R, Kheirollahi A, Davoodi J. Apaf-1: Regulation and function in cell death. Biochimie. 2017. 135: 111-1125. https://doi.org/10.1016/j.biochi.2017.02.001
  24. Tiedemann RE, Schmidt J, Keats JJ, Shi CX, Zhu YX, Palmer SE, Mao X, Schimmer AD, Stewart AK. Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and in vivo. Blood. 2009. 113: 4027-4037. https://doi.org/10.1182/blood-2008-09-179796
  25. Tomicic MT, Christmann M, Fabian K, Kaina B. Apaf-1 deficient mouse fibroblasts are resistant to MNNG and MMS-induced apoptotic death without attenuation of Bcl-2 decline. Toxicology and Applied Pharmacology. 2005. 207: 117-122. https://doi.org/10.1016/j.taap.2005.02.034
  26. Wang X, Simpson ER, Brown KA. p53: Protection against tumor growth beyond effects on cell cycle and apoptosis. Cancer Research. 2015. 75: 5001-5007. https://doi.org/10.1158/0008-5472.CAN-15-0563
  27. Yousef BA, Guerram M, Hassan HM, Hamdi AM, Zhang LY, Jiang ZZ. Pristimerin demonstrates anticancer potential in colorectal cancer cells by inducing G1 phase arrest and apoptosis and suppressing various pro-survival signaling proteins. Oncology Reports. 2016. 35: 1091-1100. https://doi.org/10.3892/or.2015.4457
  28. Yousef BA, Hassan HM, Zhang LY, Jiang ZZ. Anticancer potential and molecular targets of pristimerin: A Mini-Review. Current Cancer Drug Targets. 2017. 17: 100-108. https://doi.org/10.2174/1568009616666160112105824