톳(Hizikia fusiformis) 당단백질에 의한 HepG2 세포 증식 억제기전
Mechanism of Inhibition of HepG2 Cell Proliferation by a Glycoprotein from Hizikia fusiformis
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초록
Hizikia fusiformis, a brown alga that is widely consumed in Korea, Japan, and China, possesses a number of potentially benef icial compounds, including antioxidants and anticoagulants. However, the molecular mechanisms of H. fusiformis in hepatoma cells have not been elucidated. This study investigated the antiproliferative effect and mechanism of action of a glycoprotein from H. fusiformis (HFGP) in HepG2 human hepatoma cells. In an MTS assay, 25μg/mL HFGP inhibited the proliferation of HepG2 cells by 52.36±2.37%. HFGP caused the dose-dependent growth inhibition of HepG2 cells by inducing apoptosis and a sub-G1 phase arrest. The antiproliferative activity of HFGP was conf irmed based on the expression of several apoptosis-related proteins, which was assessed by Western blot analysis. The expressions of Fas, Fas-associated death domain protein, Bax, and Bad was signif icantly up-regulated in HFGP-treated cells, and HFGP induced the translocation of Bax to mitochondria and the release of cytochrome c into the cytosol. Therefore, HFGP might be useful in the treatment of liver cancer.
Abstract
Hizikia fusiformis, a brown alga that is widely consumed in Korea, Japan, and China, possesses a number of potentially benef icial compounds, including antioxidants and anticoagulants. However, the molecular mechanisms of H. fusiformis in hepatoma cells have not been elucidated. This study investigated the antiproliferative effect and mechanism of action of a glycoprotein from H. fusiformis (HFGP) in HepG2 human hepatoma cells. In an MTS assay, 25μg/mL HFGP inhibited the proliferation of HepG2 cells by 52.36±2.37%. HFGP caused the dose-dependent growth inhibition of HepG2 cells by inducing apoptosis and a sub-G1 phase arrest. The antiproliferative activity of HFGP was conf irmed based on the expression of several apoptosis-related proteins, which was assessed by Western blot analysis. The expressions of Fas, Fas-associated death domain protein, Bax, and Bad was signif icantly up-regulated in HFGP-treated cells, and HFGP induced the translocation of Bax to mitochondria and the release of cytochrome c into the cytosol. Therefore, HFGP might be useful in the treatment of liver cancer.
참고문헌 (30)
- Berg CP, "Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis", Cell Death Differ, 8, pp.1197~1206 (2001)
- Biliran H Jr, "Overexpression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line", Clin Cancer Res, 11, pp.6075~6086 (2005)
- Boldin MP, "Involvement of MACH, a novel MORT1", FADD-interacting protease, in Fas, Cell, pp.1996, 85[DOI]
- Bowen JM, "Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage", Support Care Cancer, 14, pp.713~731 (2006)
- Cheng WC, "Mitochondrial factors with dualrolesin death and survival", Oncogene, 25, pp.4697~4705 (2006)
- Fernandez-Luna JL, "Regulation of pro-apoptotic BH3- only proteins and its contribution to cancer progression and chemoresistance", Cell Signal, 20, pp.1921~1926 (2008)
- Galluzzi L, "Mitochondria as therapeutic targets for cancer chemotherapy", Oncogene, 25, pp.4812~4830 (2006)
- Jacks T, "Cell-cycle control and its watchman", Nature, 381, pp.643~644 (1996)
- Seon-Yong Jeong, "The role of mitochondria in apoptosis", BMB reports, 41(1), pp.11~22 (2008), 한국생화학분자생물학회
- 배송자, "참가사리 분획물의 암 예방효과", 한국식품영양과학회지, 35(4), pp.395~401 (2006), 한국식품영양과학회
- Kanno S, "Effects of naringin on cytosine arabinoside (Ara-C)-induced cytotoxicity and apoptosis in P388 cells", Life Sci, 75, pp.353~365 (2004)
- Kaufmann SH, "Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy- induced apoptosis", Cancer Res, 53, pp.3976~3985 (1993)
- 김진아, "건조방법에 따른 해조류(톳)의 생리활성 성분 및 항산화 활성의 변화", 한국식생활문화학회지, 19(2), pp.200~208 (2004), 한국식생활문화학회
- Kim KI, "Studies on the blood anticoagulant polysaccharide isolated from hot water extracts of Hizikia fusiforme", J Korean Soc Food Sci Nutr, 27, pp.1204~1210 (1998)
- 고무석, "톳 에탄올 추출물이 알코올을 투여한 흰쥐의 항산화효소활성에 미치는 영향", 한국식품영양과학회지, 31(1), pp.87~91 (2002), 한국식품영양과학회
- Kohn KW., "Molecular interaction map of the mammalian cell cycle control and DNA repair systems", Mol Biol Cell, 10, pp.2703~2734 (1999)
- Koo JG, "Blood-anticoagulant activity of fucoidans from sporophylls of Unbaria pinnatif ida, Laminaria religiosa, Hizikia fusiforme and Sargassum fulvellum in Korea", J Korean Fish Soc, 34, pp.515~520 (2001)
- Labi V, "BH3- only proteins in cell death initiation, malignant disease and anticancer therapy", Cell Death Differ, 13, pp.1325~1338 (2006)
- Lazebnik YA, "Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE", Nature, 371, pp.346~347 (1994)
- Li B, "Structural investigation of a fucoidan containing a fucose-free core from the brown seaweed, Hizikia fusiforme", Carbohydr Res, 341, pp.1135~1146 (2006)
- Lim SB, "Extraction yields of Hizikia fusiforme and Aloe vera linne by supercritical carbon dioxide and antimicrobial activity of their extracts", Korean J Food Sci Technol, 27, pp.68~73 (1995)
- Nagata S., "Apoptosis by death factor", Cell, 88, pp.355~365 (1997)
- 박기의, "톳 자숙액 에탄올 추출물의 항산화 활성", Journal of the Korean Society for Applied Biological Chemistry, 48(4), pp.435~439 (2005), 한국응용생명화학회
- Reed JC, "Bcl-2-family proteins and hematologic malignancies: history and future prospects", Blood, 111, pp.3322~3330 (2008)
- Ryu BH, "Antitumor activity of seaweeds toward sarcoma-180", Korea J Food Sci Technol, 21, pp.595~600 (1989)
- Schreiber V, "Poly(ADP-ribose): novel functions for an old molecule", Nat Rev Mol Cell Biol, 7, pp.517~528 (2006)
- Shroff EH, "Role of Bcl-2 family members in anoxia induced cell death", Cell Cycle, 6, pp.807~809 (2007)
- Singh RP, "Inositol hexaphosphate inhibits growth, and induces G1 arrest and apoptotic death of prostate carcinoma DU145 cells: modulation of CDK1-CDK-cyclin and pRb-related protein-E2F complexes", Carcinogenesis, 24, pp.555~563 (2003)
- Yin XM, "Bid, a BH3-only multi-functional molecule, is at the cross road of life and death", Gene, 369, pp.7~19 (2006)
- Zeitlin BD, "Expanding circle of inhibition: small-molecule inhibitors of Bcl-2 as anticancer cell and antiangiogenic agents", J Clin Oncol, 26, pp.4180~4188 (2008)
