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Role of Intracellular $Ca^{2+}$ Signal in the Ascorbate-Induced Apoptosis in a Human Hepatoma Cell Line


Although ascorbate (vitamin C) has been shown to have anti-cancer actions, its effect on human hepatoma cells has not yet been investigated, and thus, the exact mechanism of this action is not fully understood. In this study, the mechanism by which ascorbate induces apoptosis using HepG2 human hepatoblastoma cells is investigated. Ascorbate induced apoptotic cell death in a dose-dependent manner in the cells, was assessed through flow cytometric analysis. Contrary to expectation, ascorbate did not alter the cellular redox status, and treatment with antioxidants (N-acetyl cysteine and N,N-diphenyl-p-phenylenediamine) had no influence on the ascorbate-induced apoptosis. However, ascorbate induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration. EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the ascorbate-induced intracellular $Ca^{2+}$ increase and apoptosis, whereas dantrolene, an intracellular $Ca^{2+}$ release blocker, completely blocked these actions of ascorbate. In addition, phospholipase C (PLC) inhibitors (U-73122 and manoalide) significantly suppressed the intracellular $Ca^{2+}$ release and apoptosis induced by ascorbate. Collectively, these results suggest that ascorbate induced apoptosis without changes in the cellular redox status in HepG2 cells, and that the PLC-coupled intracellular $Ca^{2+}$ release mechanism may mediate ascorbate-induced apoptosis.

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참고문헌 (45)

  1. Amano,Y., Sakagami, H., Tanaka, T., Yamanaka, Y., Nishimoto, Y., Yamaguchi, M., and Takeda, M., Uncoupling of incorporation of ascorbic acid and apoptosis induction. Anticancer Res., 18, 2503-2506 (1998) 
  2. Baader, S. L., Bruchelt, G., Carmine, T. C., Lode, H. N., Rieth, A. G., and Niethammer, D., Ascorbic-acid-mediated iron releasefrom cellularferritinand its relation to the formation of DNA strand breaks in neuroblastoma cells. J. Cancer Res. Clin. Oncol., 120, 415-421 (1994) 
  3. Bennett, C. F., Mong, S., Wu, H. L., Clark, M. A., Wheeler, L., and Crooke, S. T., Inhibition of phosphoinositide-specific phospholipase C by manoalide. Mol. Pharmacol., 32, 587-593 (1987) 
  4. Brown, L. A. S. and Jones, D. P., The biology of ascorbic acid. In Cadenas, E, and Packer, L. (Eds.). Handbook of antioxidants. Marcel Dekker, New York, pp. 117-154, (1996) 
  5. Buettner, G. R. and Jurkiewicz, B. A., Chemistry and biochemisty of acorbic acid. In Cadenas, E, and Packer, L. (Eds.). Handbook of antioxidants, Marcel Dekker, NewYork, pp. 91-115, (1996) 
  6. Kao, T., Meyers, W .1., and Post, F., Inhibitory effects of ascorbic acid on growth of leukemic and lymphoma cell lines. Cancer Lett., 70, 101-106 (1993) 
  7. Kidd, V. J., Proteolytic activities that mediate apoptosis. Annu. Rev. Physiol., 60, 533-573 (1998) 
  8. Kornblau, S. M., The role of apoptosis in the pathogenesis, prognosis, and therapy of hematologic malignancies. Leukemia, 12, S41-46 (1998) 
  9. LaBel, C. P., Ischiopoulos, H., and Bondy, S. C., Evaluation of the probe 2',7'-dichlorofluorescin as indicator of reactive oxygen species formation and oxidative stress. Chem. Res. Toxicol., 5, 227-231 (1992) 
  10. Maramag, C., Menon, M., Balaji, K. C., Reddy, P. G., and Laxmanan, S., Effect of vitamin C on prostate cancer cells in vitro: effect on cell number viability and DNA synthesis. Prostate, 32, 188-195 (1997) 
  11. Munaron, L., Antoniotti, S., and PIa, A F., Lovisolo D. Blocking $Ca^{2+}$ entry: a way to control cell proliferation. Curr. Med. Chem., 12, 1533-1543 (2004) 
  12. Richardson,T. I., Ball, L., and Rosenfeld, T., Will an orange a day keep the doctor away? Postgrad. Med. J., 78, 292-294 (2002) 
  13. Tamayo, C. and Richardson, M. A., Vitamin C as a cancer treatment: state of the science and recommendations for research. Altern. Ther. Health Med., 9, 94-101 (2003) 
  14. Vermes, I., Haanen, Steffens, C., Nakken, H., and Reutelingsperger, C., A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J. Immunol. Methods, 184, 39-51 (1995) 
  15. Wang, X. W., Role of p53 and apoptosis in carcinogenesis. Anticancer Res., 19, 4759-4771 (1999) 
  16. Wilson, J. X., The physiological role of dehydroascorbic acid. FEBS Lett., 527, 5-9 (2002) 
  17. Scarpa, M., Stevantano, R., Viglino., and Rigo, A, Superoxide ion as reactive intermediate in the auto oxidation of ascorbate by molecular oxygen. J. Bioi. Chem., 258, 6695-6697 (1983) 
  18. Taylor, J. M. and Simpson, R. U., Inhibition of cancer cell growth by calcium channel antagonists in the athymic mouse. Cancer Res., 52, 2413-2418 (1992) 
  19. Shen, H. M., Shi, C. Y., and Ong, C. N., Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B1. Free Radic. Biol. Med., 21, 139-146 (1996) 
  20. Kamesaki, H., Mechanisms involved in chemotherapy-induced apoptosis and their implications in cancer chemotherapy. Int. J. Hematol., 68, 29-43 (1998) 
  21. Sternweis, P. C. and Smrcka, A. V., G proteins in signal transduction: the regulation of phospholipase C. Ciba Found Symp., 176, 96-106 (1993) 
  22. Bendich, A., Vitamin C safety in humans, In Packer, L. and Fuchs, J. (Eds.). Vitamin C in health and disease. Marcel Dekker Inc, New York, pp. 367-379, (1997) 
  23. Konopacka, M., Widel, M., and Rzeszowska-Wolny, J., Modifying effect of vitamins C, E and beta-carotene against gammaray- induced DNA damage in mouse cells. Mutat. Res., 417, 85-94 (1998) 
  24. Menon, M., Maramag, C., Malhotra, R. K., and Seethalakshmi, L., Effect of vitamin C on androgen independent prostate cancer cells (PC3 and Mat-Ly-Lu) in vitro: involvement of reactive oxygen species-effect on cell number, viability and DNA synthesis. Cancer Biochem. Biophys., 16, 17-30 (1998) 
  25. Ehrlich, B. E., Kaftan, E., Bezprozvannaya, S., and Bezprozvanny, I., The pharmacology of intracellular $Ca^{2+}$ release channels. Trends Pharmacol. Sci., 15, 145-149 (1994) 
  26. Tauchi, H. and Sawada, S., Suppression of gamma- and neutron-induced neoplastic transformation by ascorbic acid in Balb/c 3T3 cells. Int. J. Radiat. Biol., 63, 369-374 (1993) 
  27. Yoshida, J., Ishibashi, T., and Nishio, M., Antiproliferative effect of $Ca^{2+}$ channel blockers on human epidermoid carcinoma A431 cells. Eur. J. Pharmacol., 472, 23-31 (2003) 
  28. Song, J. H., Shin, S. H., Wang, W., and Ross, G. M., Involvement of oxidative stress in ascorbate-induced proapoptotic death of PC12 cells. Exp. Neurol., 169, 425-437 (2001) 
  29. McConkey, D. J. and Orrenius, S., The role of calcium in the regulation of apoptosis. Biochem. Biophys. Res. Commun., 239, 357-366 (1997) 
  30. Crompton, N. E., Programmed cellular response in radiation oncology. Acta Oncol., 37, 1-49 (1998) 
  31. Grynkiewicz, G., Poene, M., and Tsien, R. Y., A new generation of $Ca^{2+}$ indicators with greatly improved fluorescence properties. J. Biol. Chem., 260, 3440-3450 (1985) 
  32. Li, S. W., Westwick, J., and Poll, C. T., Receptor-operated Ca2 + influx channels in leukocytes: a therapeutic target? Trends Pharmacal. Sci., 23, 63-70 (2002) 
  33. Lowe, S. Wand Lin, A. W, Apoptosis in cancer. Carcinogenesis, 21, 485-495 (2000) 
  34. Singer, W. D., Brown, H. A., and Sternweis, P. C., Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D. Annu. Rev. Biochem., 66, 475-509 (1997) 
  35. Jambrina, E., Alonso, R., Alcalde, M., del Carmen Rodriguez, M., Serrano, A, Martinez-A, C., Garcia-Sancho, J., and Izquierdo, M., Calcium influx through receptor-operated channel induces mitochondria-triggered paraptotic cell death. J. Bioi. Chem., 278, 14134-14145 (2003) 
  36. Milner, A. E., Levens, J. M., and Gregory, C. D., Flow cytometric methods of analyzing apoptotic cells. Methods Mol. Biol., 80, 347-354 (1998) 
  37. Kang, J. S., Cho, D., Kim, Y. I., Hahm, E, Yang, Y., Kim, D., Hur, D., Park, H., Bang, S., Hwang, Y. I., and Lee, W J., LAscorbic acid (vitamin C) induces the apoptosis of B16 murine melanoma cells via a caspase-8-independent pathway. Cancer Immunol. Immunother., 52, 693-698 (2003) 
  38. Lee, Y S. and Wurster, R. D., Potentiation of anti-proliferative effect of nitroprusside by ascorbate in human brain tumor cells. Cancer Lett., 78, 9-23 (1994) 
  39. Lee, K. W., Lee, H. J., Sum, Y. J., and Lee, C. Y., Vitamin C and cancer chemoprevention: reappraisal. Am. J. Clin. Nutr., 78, 1074-1078 (2003) 
  40. Gardiner, N. S. and Duncan, J. R., Inhibition of murine melanoma growth by sodium ascorbate. J. Nutr., 119, 586-590 (1989) 
  41. Hughes, A. R. and Putney, J. W. Jr., Inositol phosphate formation and its relationship to calcium signaling. Environ. Health Perspect., 84, 141-147 (1990) 
  42. Jackisch, C., Hahm, H. A., Tombal, B., McCloskey, D., Butash, K., Davidson, N. E., and Denmeade, S. R., Delayed micromolar elevation in intracellular calcium precedes induction of apoptosis in thapsigargin-treated breast cancer cells. Clin. Cancer Res., 6, 2844-2850 (2000) 
  43. Jin, W., Lo, T. M., Loh, H. H., and Thayer, S. A., U73122 inhibits phospholipase C-dependent calcium mobilization in neuronal cells. Brain Res., 642, 237-243 (1994) 
  44. Song, Z. and Steller, H., Death by design: mechanism and control of apoptosis. Trends Cell. BioI., 9, 49-52 (1999) 
  45. Yasukawa, M., Terashima, T., and Seki, M., Radiation induced transformation of C3H10T1/2 cells is suppressed by ascorbic acid. Radiat. Res., 120, 456-467 (1989 ) 

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