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Anti-carcinogenic actions of glycoprotein conjugated with isoflavones from submerged-liquid culture of Agaricus blazei mycelia through reciprocal expression of Bcl-2 and Bax proteins

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충북대학교 동물의학연구소 (Research Institute of Veterinary Medicine, Chungbuk National University)
초록

Glycoproteins isolated from fruit bodies and mycelial cultures of mushrooms exhibit anti-carcinogenic actions in human cancer cells and animal tumor cells by induction of apoptosis. Here, we report that isoflavone-conjugated glycoproteins (designate Gluvone), exhibit strong anti-carcinogenic effects on human breast cancer MCF-7 cells by induction of apoptosis. Gluvone with 9.4 kDa of molecular weight was isolated from submerged-liquid culture of Agaricus blazei mycelia (ABM) in soy flake-containing liquid medium. MCF-7 cells were incubated with various amounts of Gluvone (0~250 μM) for a period of 6 days. Gluvone exhibited anti-proliferative actions in a dose-dependent manner and 62% growth inhibition at 200 μM for 4 days relative to control. Hoechst 33258 staining analysis revealed that Gluvone induced formation of apoptotic bodies. Gluvone was associated with down-regulation of anti-apoptotic Bcl-2 protein expression as well as up-regulation of pro-apoptotic Bax protein expression. Gluvone treatment induced proteolytic activation of caspase-9 and caspase-3 through cytochrome c release from mitochondria to cytosol as well as concomitant degradation of poly (ADP-ribose) polymerase (PARP). In addition, Gluvone induced activation of caspase-8. Taken all together, these results indicate that the anti-proliferative effect of Gluvone is associated with induction of apoptotic cell death through the mitochondrial dysfunction pathway mediated by enhancement of Bax protein expression and suppression of Bcl-2 protein expression.

저자
  • Young-Suk Kim(HK Biotech, Co. Ltd., Jinju 660-844, Korea)
  • Boh-Hyun Kim(Department of Applied Chemistry, College of Agriculture and Life Science, and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Korea)
  • Gon-Sup Kim(Laboratory of Biochemistry, School of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Korea)
  • Joung-Soon Jang(Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul 156-576, Korea)
  • So-Young Kim(Department of Food and Nutrition, International University of Korea, Jinju 660-759, Korea)
  • Byeong-Dae Choi(Department of Marine Food and Life Science Engineering, College of Marine Science, Gyeongsang National University, Tongyoung 650-160, Korea)
  • Jeong-Ok Kim(HK Biotech, Co. Ltd., Jinju 660-844, Korea)
  • Yeong-Lae Ha(Department of Applied Chemistry, College of Agriculture and Life Science, and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Korea) Corresponding author