Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Plant sterols have shown potent anti-proliferative effects andapoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has notbeen investigated. In the present study, we assessed whetherthe stigmasterol isolated from Navicula incerta possessesapoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated theexpression of pro-apoptotic gene expressions (Bax, p53) whiledown-regulating the anti-apoptotic genes (Bcl-2). Probably viamitochondrial apoptosis signaling pathway. With the inductionof apoptosis caspase-8, 9 were activated. The DNAdamage and increase in apoptotic cell numbers were observedthrough Hoechst staining, annexin V staining and cell cycleanalysis. According to these results, we can suggest that thestigmasterol shows potent apoptosis inductive effects and hasthe potential to be tested as an anti-cancer therapeutic againstliver cancer.
Abstract
Plant sterols have shown potent anti-proliferative effects andapoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has notbeen investigated. In the present study, we assessed whetherthe stigmasterol isolated from Navicula incerta possessesapoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated theexpression of pro-apoptotic gene expressions (Bax, p53) whiledown-regulating the anti-apoptotic genes (Bcl-2). Probably viamitochondrial apoptosis signaling pathway. With the inductionof apoptosis caspase-8, 9 were activated. The DNAdamage and increase in apoptotic cell numbers were observedthrough Hoechst staining, annexin V staining and cell cycleanalysis. According to these results, we can suggest that thestigmasterol shows potent apoptosis inductive effects and hasthe potential to be tested as an anti-cancer therapeutic againstliver cancer.
참고문헌 (25)
- Spolaore, P., "Commercial applications of microalgae", J. Biosci. Bioeng, 101, pp.87~96 (2006)
- Plaza, M., "Inovative natural functional ingredients from Microalgae", J. Agric. Food Chem, 57, pp.7159~7170 (2009)
- Kang, K. H., "Protective effects of protein hydrolysate from Marine Microalgae Navicula incerta on ethanol-induced toxicity in HepG2", CYP2E1 cells, 2011, pp.132, 677~685
- Ryan, E., "Phytosterol oxidation products: their formation, occurance and biological effects", Food Rev. Int, 25, pp.157~174 (2009)
- Awad, A. B., "Phytosterols as anticancer dietary components: evidence and mechanism of action", J. Nutr, 130, pp.2127~2130 (2000)
- Von Holtz, R. L., "β-Sitosterol sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells", Nutr. Cancer, 32, pp.8~12 (1998)
- Downie, A., "Effect of phytosterols on MDA-MB-231 human breast cancer cell growth", FASEB J, 13, pp.A333~ (1999)
- Yvonne C. O’Callaghan, "Cytotoxicity and apoptosis effects of the oxidized derivatives of stigmasterol in the U937 human monocytic cell line", J. Agric. Food Chem, 58(19), pp.10793~10798 (2010)
- Raicht, R. F., "Protective effect of plant sterols against chemically induced colon tumors in rats", Cancer Res, 40, pp.403~405 (1980)
- Hetz, C. A., "Beyond apoptosis: non-apoptotic cell death in physiology and disease", Biochem. Cell Biol, 83, pp.579~588 (2005)
- Gerl, R., "Apoptosis in the development and treatment of cancer", Carcinogenesis, 26, pp.263~270 (2005)
- Haimovitz-Friedman, A., "Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis", J. Exp. Med, 180, pp.525~535 (1994)
- Santana, P., "Acid sphingomyelinase deficient lymphoblasts and mice are defective in radiation induced apoptosis", Cell, 86, pp.189~199 (1996)
- Narula, J., "Apoptosis and the heart", Chest, 112, pp.1358~1362 (1997)
- suppresses pro-inflammatory responses by blocking NF-κB and MAPK signaling pathways in activated microglia, "Eur. J. Pharmacol", 2011, 608~616
- Ryu, B., "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, pp.192~201 (2009)
- Awad, A. B., "Beta-sitosterols inhibits HT-29 human colon cancer cell growth and alters membrane lipids", Anticancer Res, 16, pp.2797~2804 (1996)
- Trouillas, P., "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, pp.1141~1149 (2005)
- Vermes, I., "A novelassay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V", J. Immunol. Methods, 184, pp.39~51 (1995)
- Antonsson, B., "Bax and other pro-apoptotic Bcl-2 family ‘‘killer-proteins” and their victim the mitochondrion", Cell Tissue Res, 306, pp.347~361 (2001)
- Zornig, M., "Apoptosis regulators and their role in tumorigenesis", Biochem. Biophys. Acta, 1551, pp.1~37 (2001)
- Roy, N., "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases", EMBO J, 16, pp.6914~6925 (1997)
- Deveraux, Q. L., "IAP family proteins suppressors of apoptosis", Genes Dev, 13, pp.239~252 (1999)
- 황유진, "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, 2013, pp.46(12), 611~616[DOI]
- Caihong Zhou, "Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells", BMB Reports, 46(2), pp.113~118 (2013), 생화학분자생물학회