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Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells

  • Hahm, Sahng-Wook (Department of Animal Sciences, Colorado State University) ;
  • Park, Jieun (Integrative Research Support Center, The Catholic University of Korea) ;
  • Park, Kun-Young (Department of Food Science and Nutrition, Pusan National University) ;
  • Son, Yong-Suk (Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Han, Hyungchul (Department of Animal Sciences, Colorado State University)
  • Received : 2015.10.30
  • Accepted : 2016.01.05
  • Published : 2016.03.31

Abstract

Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF ($100{\mu}g/mL$) significantly induced (P<0.05) the G1 phase cell cycle arrest. Additionally, the apoptotic cell population was greater (P<0.05) in OHF ($200{\mu}g/mL$) treated AGS cells when compared to the control. The expression of genes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells.

Acknowledgement

Supported by : Korea University

References

  1. Acuna UM, Atha DE, Ma J, Nee MH, Kennelly EJ. 2002. Antioxidant capacities of ten edible North American plants. Phytother Res 16: 63-65.
  2. Kim J, Jho KH, Choi YH, Nam SY. 2013. Chemopreventive effect of cactus (Opuntia humifusa) extracts: radical scavenging activity, pro-apoptosis, and anti-inflammatory effect in human colon (SW480) and breast cancer (MCF7) cells. Food Funct 4: 681-688. https://doi.org/10.1039/c3fo30287c
  3. Goldstein G, Nobel PS. 1994. Water relations and low-temperature acclimation for cactus species varying in freezing tolerance. Plant Physiol 104: 675-681. https://doi.org/10.1104/pp.104.2.675
  4. Hahm SW, Park J, Son YS. 2011. Opuntia humifusa stems lower blood glucose and cholesterol levels in streptozotocin-induced diabetic rats. Nutr Res 31: 479-487. https://doi.org/10.1016/j.nutres.2011.05.002
  5. Lee JA, Jung BG, Kim TH, Lee SG, Park YS, Lee BJ. 2013. Dietary feeding of Opuntia humifusa inhibits UVB radiation-induced carcinogenesis by reducing inflammation and proliferation in hairless mouse model. Photochem Photobiol 89: 1208-1215. https://doi.org/10.1111/php.12113
  6. Park J, Hahm SW, Son YS. 2011. Effects of cheonnyuncho (Opuntia humifusa) seeds treatment on the mass, quality, and the turnover of bone in ovariectomized rats. Food Sci Biotechnol 20: 1517-1524. https://doi.org/10.1007/s10068-011-0210-7
  7. Hahm SW, Park J, Oh SY, Lee CW, Park KY, Kim H, Son YS. 2015. Anticancer properties of extracts from Opuntia humifusa against human cervical carcinoma cells. J Med Food 18: 31-44. https://doi.org/10.1089/jmf.2013.3096
  8. Hahm SW, Park J, Son YS. 2010. Opuntia humifusa partitioned extracts inhibit the growth of U87MG human glioblastoma cells. Plant Foods Hum Nutr 65: 247-252. https://doi.org/10.1007/s11130-010-0188-y
  9. Nabel EG. 2003. Cardiovascular disease. N Engl J Med 349: 60-72. https://doi.org/10.1056/NEJMra035098
  10. Gebhardt R. 2003. Variable influence of kaempferol and myricetin on in vitro hepatocellular cholesterol biosynthesis. Planta Med 69: 1071-1074. https://doi.org/10.1055/s-2003-45184
  11. Heidari S, Akrami H, Gharaei R, Jalili A, Mahdiuni H, Golezar E. 2014. Anti-tumor activity of Ferulago angulata Boiss. extract in gastric cancer cell line via induction of apoptosis. Iran J Pharm Res 13: 1335-1345.
  12. Tan J, Qi H, Ni J. 2015. Extracts of endophytic fungus XKCs03 from Prunella vulgaris L. spica inhibit gastric cancer in vitro and in vivo. Oncol Lett 9: 945-949. https://doi.org/10.3892/ol.2014.2722
  13. Zhao X, Kim SY, Park KY. 2013. Bamboo salt has in vitro anticancer activity in HCT-116 cells and exerts anti-metastatic effects in vivo. J Med Food 16: 9-19. https://doi.org/10.1089/jmf.2012.2316
  14. Schmittgen TD, Livak KJ. 2008. Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3: 1101-1108. https://doi.org/10.1038/nprot.2008.73
  15. Lee HS, Cho HJ, Yu R, Lee KW, Chun HS, Park JH. 2014. Mechanisms underlying apoptosis-inducing effects of kaempferol in HT-29 human colon cancer cells. Int J Mol Sci 15: 2722-2737. https://doi.org/10.3390/ijms15022722
  16. Woo Y, Shin SY, Hyun J, Lee SD, Lee YH, Lim Y. 2012. Flavanones inhibit the clonogenicity of HCT116 cololectal cancer cells. Int J Mol Med 29: 403-408.
  17. Alonso-Castro AJ, Ortiz-Sanchez E, Garcia-Regalado A, Ruiz G, Nunez-Martinez JM, Gonzalez-Sanchez I, Quintanar-Jurado V, Morales-Sanchez E, Dominguez F, Lopez-Toledo G, Cerbon MA, Garcia-Carranca A. 2013. Kaempferitrin induces apoptosis via intrinsic pathway in HeLa cells and exerts antitumor effects. J Ethnopharmacol 145: 476-489. https://doi.org/10.1016/j.jep.2012.11.016
  18. Grana X, Reddy EP. 1995. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11: 211-219.
  19. Drobnjak M, Osman I, Scher HI, Fazzari M, Cordon-Cardo C. 2000. Overexpression of cyclin D1 is associated with metastatic prostate cancer to bone. Clin Cancer Res 6: 1891-1895.
  20. Sun S, Zimmet JM, Toselli P, Thompson A, Jackson CW, Ravid K. 2001. Overexpression of cyclin D1 moderately increases ploidy in megakaryocytes. Haematologica 86: 17-23.
  21. Ishii Y, Pirkmaier A, Alvarez JV, Frank DA, Keselman I, Logothetis D, Mandeli J, O'Connell MJ, Waxman S, Germain D. 2006. Cyclin D1 overexpression and response to bortezomib treatment in a breast cancer model. J Natl Cancer Inst 98: 1238-1247. https://doi.org/10.1093/jnci/djj334
  22. Schwartz GK, Shah MA. 2005. Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol 23: 9408-9421. https://doi.org/10.1200/JCO.2005.01.5594
  23. Sherr CJ, Roberts JM. 1999. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13: 1501-1512. https://doi.org/10.1101/gad.13.12.1501
  24. Rihani A, Vandesompele J, Speleman F, Van Maerken T. 2015. Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma. Cancer Cell Int 15: 76. https://doi.org/10.1186/s12935-015-0224-y
  25. Chao DT, Korsmeyer SJ. 1998. BCL-2 family: regulators of cell death. Annu Rev Immunol 16: 395-419. https://doi.org/10.1146/annurev.immunol.16.1.395
  26. Adams JM, Cory S. 2007. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26: 1324-1337. https://doi.org/10.1038/sj.onc.1210220
  27. Lin Y, Kokontis J, Tang F, Godfrey B, Liao S, Lin A, Chen Y, Xiang J. 2006. Androgen and its receptor promote bax-mediated apoptosis. Mol Cell Biol 26: 1908-1916. https://doi.org/10.1128/MCB.26.5.1908-1916.2006
  28. Shafi G, Munshi A, Hasan TN, Alshatwi AA, Jyothy A, Lei DK. 2009. Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa. Cancer Cell Int 9: 29. https://doi.org/10.1186/1475-2867-9-29
  29. Sawada M, Nakashima S, Banno Y, Yamakawa H, Hayashi K, Takenaka K, Nishimura Y, Sakai N, Nozawa Y. 2000. Ordering of ceramide formation, caspase activation, and Bax/Bcl-2 expression during etoposide-induced apoptosis in C6 glioma cells. Cell Death Differ 7: 761-772. https://doi.org/10.1038/sj.cdd.4400711
  30. Green DR, Kroemer G. 2009. Cytoplasmic functions of the tumour suppressor p53. Nature 458: 1127-1130. https://doi.org/10.1038/nature07986
  31. He Y, Chen W, Hu Y, Luo B, Wu L, Qiao Y, Mo Q, Xu R, Zhou Y, Ren Z, Zuo Z, Deng J, Peng G, He W, Wei Y. 2015. E. adenophorum induces cell cycle and apoptosis of renal cells through mitochondrial pathway and caspase activation in Saanen goat. PLoS One 10: e0138504. https://doi.org/10.1371/journal.pone.0138504
  32. Agarwal ML, Agarwal A, Taylor WR, Stark GR. 1995. p53 controls both the $G_2/M$ and the $G_1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc Natl Acad Sci USA 92: 8493-8497. https://doi.org/10.1073/pnas.92.18.8493