본문 바로가기
KERD
논문KCI 등재

Vitamin C Induces Apoptosis in Human Colon Cancer Cell Line, HCT-8 Via the Modulation of Calcium Influx in Endoplasmic Reticulum and the Dissociation of Bad from 14-3-3β

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

It has been reported that vitamin C plays an effective role in the treatment and prevention of cancer, but its specific mechanisms are still largely unknown. The incidence of colon cancer is now increasing in Korea. Therefore, we have examined here the effect of vitamin C on the induction of the apoptosis on colon cancer and its related mechanisms. We have found that remarkable increase of the apoptosis and the calcium influx in endoplasmic reticulum (ER) in human colon cancer cell line, HCT-8. However, vitamin C-induced apoptosis was effectively inhibited by the pre-treatment of BAPTA-AM (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid), which is well-known as a calcium specific chelator. During the apoptosis, we found the increase of the translocation of Bad to mitochondria from cytosol, after releasing from 14-3-3β. In this process, the expression of Bax,a well-known pro-apoptotic protein, was also increased. Taken together, vitamin C induces apoptosis of colon cancer cell line, HCT-8 through the increase of 1) the calcium influx in endoplasmic reticulum (ER), 2) the translocation of Bad to mitochondria, and 3) the expression of Bax.

Abstract

It has been reported that vitamin C plays an effective role in the treatment and prevention of cancer, but its specific mechanisms are still largely unknown. The incidence of colon cancer is now increasing in Korea. Therefore, we have examined here the effect of vitamin C on the induction of the apoptosis on colon cancer and its related mechanisms. We have found that remarkable increase of the apoptosis and the calcium influx in endoplasmic reticulum (ER) in human colon cancer cell line, HCT-8. However, vitamin C-induced apoptosis was effectively inhibited by the pre-treatment of BAPTA-AM (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid), which is well-known as a calcium specific chelator. During the apoptosis, we found the increase of the translocation of Bad to mitochondria from cytosol, after releasing from 14-3-3β. In this process, the expression of Bax,a well-known pro-apoptotic protein, was also increased. Taken together, vitamin C induces apoptosis of colon cancer cell line, HCT-8 through the increase of 1) the calcium influx in endoplasmic reticulum (ER), 2) the translocation of Bad to mitochondria, and 3) the expression of Bax.

참고문헌 (35)

  1. Kang, J. S., "L-ascorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway", Cancer Immunol. Immunother, 52, pp.693~698 (2003)
  2. Kang, J. S, "Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake", J. Cell. Physiol, 204, pp.192~197 (2005)
  3. Kim, J. E, "Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity", Int. J. Mol. Med, 22, pp.651~655 (2008)
  4. Hahm, E., "The molecular mechanisms of vitamin C on cell cycle regulation in B16F10 murine melanoma", J. Cell. Biochem, 102, pp.1002~1010 (2007)
  5. Lee, S. K., "Vitamin C suppresses proliferation of the human melanoma cell SK-MEL-2 through the inhibition of cyclooxygenase-2 (COX-2) expression and the modulation of insulin-like growth factor II (IGF-II) production", J. Cell. Physiol, 216, pp.180~188 (2008)
  6. 김하나, "Vitamin C down-regulates VEGF production in B16F10 murine melanoma cells via the suppression of p42", 44 MAPK activation, 201103, pp.112(3), 894~901[DOI]
  7. 김영석, "Vitamin C downregulates interleukin-18 production by increasing reactive oxygen intermediate and mitogen-activated protein kinase signalling in B16F10 murine melanoma cells", MELANOMA RESEARCH, 13, pp.549~554, LIPPINCOTT WILLIAMS & WILKINS
  8. Zhang, J., "Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: role of nutrition transition", Eur. J. Cancer Prev, 21, pp.480~489 (2012)
  9. Ruiz de Erenchun, F, "The role of new agents in the treatment of colorectal cancer", Oncology, 68, pp.162~ (2005)
  10. Inoue, Y., "Schedule-dependent cytotoxicity of 5-fluorouracil and irinotecan in a colon cancer cell line", J. Gastroenterol, 41, pp.1149~1157 (2006)
  11. Pallis, A. G., "Adjuvant chemotherapy for colon cancer", Anticancer Res., 26, pp.4809~4815 (2006)
  12. Jacoby, R. F, "Chemoprevention of spontaneous intestinal adenomas in the Apc Min mouse model by the nonsteroidal anti-inflammatory drug piroxicam", Cancer Res, 56, pp.710~714 (1996)
  13. Liou, J. Y., "Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon", Cancer Res, 67, pp.3185~1391 (2007)
  14. McDonnell, M. A, "Caspase-9 is activated in a cytochrome c-independent manner early during TNFalpha-induced apoptosis in murine cells", Cell Death Differ, 10, pp.1005~1015 (2003)
  15. Katoh, I., "Dimerization and processing of procaspase-9 by redox stress in mitochondria", J. Biol. Chem, 279, pp.15515~15523 (2004)
  16. Wiley, S. R., "Identification and characterization of a new member of the TNF family that induces apoptosis", Immunity, 3, pp.673~682 (1995)
  17. Wang, S, "and apoptosis induction by TNF-family death receptors", Oncogene, 22, pp.8628~8633 (2003)
  18. von Haefen, C., "Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells", Oncogene, 21, pp.4009~4019 (2002)
  19. Torkin, R., "Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma", Mol. Cancer Ther, 4, pp.1~11 (2005)
  20. Boya, P., "Endoplasmic reticulum stress-induced cell death requires mitochondrial membrane permeabilization", Cell Death Differ, 9, pp.465~467 (2002)
  21. Li, J., "Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53", J. Biol. Chem, 281, pp.7260~7270 (2006)
  22. Zhang, D., "Bax and the mitochondrial permeability transition cooperate in the release of cytochrome c during endoplasmic reticulum-stress-induced apoptosis", Cell Death Differ, 14, pp.703~715 (2007)
  23. Hung, J. H., "Endoplasmic reticulum stress stimulates the expression of cyclooxygenase-2 through activation of NF-kappaB and pp38 mitogen-activated protein kinase", J. Biol. Chem, 279, pp.46384~46392 (2004)
  24. Szegezdi, E., "Mediators of endoplasmic reticulum stress-inducedapoptosis", EMBO Rep, 7, pp.880~885 (2006)
  25. Breckenridge, D. G, "Regulation of apoptosis by endoplasmic reticulum pathways", Oncogene, 22, pp.8608~8618 (2003)
  26. Shou, Y., "Calcineurin-mediated Bad translocation regulates cyanide-induced neuronal apoptosis", Biochem. J, 379, pp.805~813 (2004)
  27. Cardoso, S. M, "The role of calcineurin in amyloid-beta-peptides-mediated cell death", Brain Res, 1050, pp.1~7 (2005)
  28. Rapp, U. R., "BAD association with membranes is regulated by Raf kinases and association with 14-3-3 proteins", Adv. Enzyme Regul, 47, pp.281~285 (2007)
  29. Claerhout, S., "AKT delays the early-activated apoptotic pathway in UVB-irradiated keratinocytes via BAD translocation", J. Invest. Dermatol, 127, pp.429~438 (2007)
  30. Levine, M., "Determination of optimal vitamin C requirements in humans", Am. J. Clin. Nutr, 62(6), pp.1347S~1356S (1995)
  31. Wolucka, B. A., "Mycobacterium tuberculosis possesses a functional enzyme for the synthesis of vitamin C, L-gulono-1,4-lactone dehydrogenase", FEBS J, 273, pp.4435~4445 (2006)
  32. Härtel, C., "Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes", Cytokine, 27, pp.101~106 (2004)
  33. Hartel, C., "Immunomodulatory effect of vitamin C on intracytoplasmic cytokine production in neonatal cord blood cells", Neonatology, 91, pp.54~60 (2007)
  34. Lin, S. Y, "Sodium ascorbate inhibits growth via the induction of cell cycle arrest and apoptosis in human malignant melanoma A375.S2 cells", Melanoma Res, 16, pp.509~519 (2006)
  35. Boyer, J., "Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan", Clin. Cancer R, 10, pp.2158~2167 (2004)

관련 논문AI추천

이 간행물의 다른 논문 (7건)