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KMID : 1004820140150040200
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Journal of Biomedical Research
2014 Volume.15 No. 4 p.200 ~ p.206
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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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Kim Young-Suk
Kim Boh-Hyun
Kim Gon-Sup
Jang Joung-Soon
Kim So-Young
Choi Byeong-Dae
Kim Jeong-Ok
Ha Yeong-Lae
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Abstract
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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 anticarcinogenic 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 proapoptotic 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 antiproliferative 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.
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KEYWORD
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Agaricus blazei mycelium (ABM), apoptosis, caspase 3, human breast cancer MCF-7 cells, isoflavoneconjugated glycoproteins (Gluvone)
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