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Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells

  • Kim, Young-Sang (Department of Chemistry, Pukyong National University) ;
  • Li, Xi-Feng (Chemical Biology Center of YanBian University) ;
  • Kang, Kyong-Hwa (Marine Bioprocess Research Center, Pukyong National University) ;
  • Ryu, BoMi (School of Pharmacy, The University of Queensland) ;
  • Kim, Se Kwon (Marine Bioprocess Research Center, Pukyong National University)
  • Received : 2013.07.02
  • Accepted : 2013.09.23
  • Published : 2014.08.31

Abstract

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

Keywords

References

  1. Spolaore, P., Joannis-Cassan, C., Duran, E. and Isambert, A. (2006) Commercial applications of microalgae. J. Biosci. Bioeng. 101, 87-96. https://doi.org/10.1263/jbb.101.87
  2. Plaza, M., Herrero M., Cifuentes A. and Ibanez E. (2009) Inovative natural functional ingredients from Microalgae. J. Agric. Food Chem. 57, 7159-7170. https://doi.org/10.1021/jf901070g
  3. Kang, K. H., Qian, Z. J., Ryu, B., Kim, D. and Kim, S. K. (2011) Protective effects of protein hydrolysate from Marine Microalgae Navicula incerta on ethanol-induced toxicity in HepG2/CYP2E1 cells. Food Chem. 132, 677-685.
  4. Ryan, E., McCarthy, F., Maguire, A. and O'Brien, N. (2009) Phytosterol oxidation products: their formation, occurance and biological effects. Food Rev. Int. 25, 157-174. https://doi.org/10.1080/87559120802682797
  5. Awad, A. B. and Fink, C. S. (2000) Phytosterols as anticancer dietary components: evidence and mechanism of action. J. Nutr. 130, 2127-2130.
  6. Von Holtz, R. L., Fink, C. S. and Hennessey, T. (1998) $\beta$-Sitosterol sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells. Nutr. Cancer. 32, 8-12. https://doi.org/10.1080/01635589809514709
  7. Downie, A., Fink C. S. and Awad, A. B. (1999) Effect of phytosterols on MDA-MB-231 human breast cancer cell growth. FASEB J. 13, A333 (abs.).
  8. Yvonne C. O'Callaghan, David A. Foley, Niamh M. O'Connell, Florence O. McCarthy, Anita R. Maguire, and Nora M. O'brien. (2010) Cytotoxicity and apoptosis effects of the oxidized derivatives of stigmasterol in the U937 human monocytic cell line. J. Agric. Food Chem. 58, 19, 10793-10798. https://doi.org/10.1021/jf1023017
  9. Raicht, R. F., Cohen, L. I., Fazzini, E. P., Sarwal, A. N. and Takahashi, M. (1980) Protective effect of plant sterols against chemically induced colon tumors in rats. Cancer Res. 40, 403-405.
  10. Hetz, C. A., Torres, V. and Quest, A. F. (2005) Beyond apoptosis: non-apoptotic cell death in physiology and disease. Biochem. Cell Biol. 83, 579-588. https://doi.org/10.1139/o05-065
  11. Gerl, R. and Vaux, D. L. (2005) Apoptosis in the development and treatment of cancer. Carcinogenesis 26, 263-270.
  12. Haimovitz-Friedman, A., Kan, C. C., Enleiter, D., Persaud, R. S., McLoughlin, M., Fuks, Z. and Kolesnick, R. N. (1994) Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J. Exp. Med. 180, 525-535. https://doi.org/10.1084/jem.180.2.525
  13. Santana, P., Pena, L. A. and Haimovitz-Friedman, A. (1996) Acid sphingomyelinase deficient lymphoblasts and mice are defective in radiation induced apoptosis. Cell 86, 189-199. https://doi.org/10.1016/S0092-8674(00)80091-4
  14. Narula, J., Kharbanda, S. and Khaw, B-A. (1997) Apoptosis and the heart. Chest 112, 1358-1362. https://doi.org/10.1378/chest.112.5.1358
  15. Himaya, S. W. A., Ryu, B., Qian, Z. J., Li, Y. and Kim, S. K. (2011) 1-(5-bromo-2-hydroxy-4-methoxyphenyl)ethanone [SE1] suppresses pro-inflammatory responses by blocking NF-${\kappa}B$ and MAPK signaling pathways in activated microglia. Eur. J. Pharmacol. 670, 608-616.
  16. Ryu, B., Li, Y., Qian, Z. J., Kim, M. M. and Kim, S. K. (2009) Differentiation of human osteosarcoma cells by isolated phlorotannins is subtly linked to COX-2, iNOS, MMPs, and MAPK signaling: Implication for chronic articular disease. Chem. Biol. Interact. 179, 192-201. https://doi.org/10.1016/j.cbi.2009.01.006
  17. Awad, A. B., Chen, Y. C., Fink, C. S. and Hennessey, T. (1996) Beta-sitosterols inhibits HT-29 human colon cancer cell growth and alters membrane lipids. Anticancer Res. 16, 2797-2804.
  18. Trouillas, P., Corbiere, C., Liagre, B., Duroux, J. L. and Beneytout, J. L. (2005) Structure-function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modeling approach of natural molecules structurally close to diosgenin. Bioorg. Med. Chem. 13, 1141-1149. https://doi.org/10.1016/j.bmc.2004.11.031
  19. Vermes, I., Haanen, C., Steffens-Nakken, H. and Reutellingsperger, C. (1995). A novelassay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J. Immunol. Methods 184, 39-51. https://doi.org/10.1016/0022-1759(95)00072-I
  20. Antonsson, B. (2001) Bax and other pro-apoptotic Bcl-2 family ''killer-proteins" and their victim the mitochondrion. Cell Tissue Res. 306, 347-361. https://doi.org/10.1007/s00441-001-0472-0
  21. Zornig, M., Hueber, A., Baum, W. and Evan, G. (2001) Apoptosis regulators and their role in tumorigenesis. Biochem. Biophys. Acta. 1551, 1-37.
  22. Roy, N., Deveraux, O. L., Takahashi, R., Salvesen, G. S. and Reed, J. C. (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J. 16, 6914-6925. https://doi.org/10.1093/emboj/16.23.6914
  23. Deveraux, Q. L. and Reed, J. C. (1999) IAP family proteins suppressors of apoptosis. Genes Dev. 13, 239-252. https://doi.org/10.1101/gad.13.3.239
  24. Hwang, Y. J., Lee, E. J., Kim, H. R. amd Hwang, K. A. (2013) Molecular mechanisms of luteolin-7-O-glucoside-induced growth inhibition on human liver cancer cells: G2/M cell cycle arrest and caspase-independent apoptotic signaling pathways. BMB Rep. 46, 611-616. https://doi.org/10.5483/BMBRep.2013.46.12.133
  25. Zhou, C., Shen Q., Xue, J., Ji, C. and Chen, J. (2013) Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells. BMB Rep. 46, 113-118. https://doi.org/10.5483/BMBRep.2013.46.2.150

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