Park Bong S, Baek Soo J, Song Ki H, Kim Ki-Ho, Jeong Soo J, Jeong Min H, Seo Su Y, Lee Sung W, Yoo Ki S, Yoo Young H
Department of Oral Anatomy and Cell Biology, Pusan National University College of Dentistry, Pusan 602-739, South Korea.
Nutr Cancer. 2002;42(2):248-55. doi: 10.1207/S15327914NC422_15.
Although genistein has been demonstrated to induce apoptosis of various cells, there is no report of its effect on mast cell proliferation. Here we show that genistein reduced the viability of mast cell tumor cell lines, p815 and RBL-2H, but not of a human mast cell line, HMC-1. Further investigation on its growth-inhibitory mechanism was undertaken on p815 mastocytoma cells. Genistein induced G2/M arrest and subsequent apoptotic death. p815 cells undergoing apoptosis showed many apoptotic manifestations, such as reduction of mitochondrial membrane potential, release of cytochrome c to cytosol, translocation of apoptosis-inducing factor to nucleus, activation of caspase-3, nuclear condensation, and generation of DNA fragmentation. Genistein treatment resulted in the increase of Bax expression and its translocation into mitochondria, whereas expression levels of Bcl-2 remained unchanged. Proteasome activity decreased at the early time points after genistein treatment, but thereafter it fluctuated at increased levels. A proteasome inhibitor, lactacystin, potentiated the induction of apoptosis. Taken together, genistein-induced apoptosis of p815 mastocytoma cells is at least in part mediated by proteasome, Bax, apoptosis-inducing factor, and caspase and augmented by cotreatment with a proteasome inhibitor, lactacystin.
尽管已证明染料木黄酮可诱导多种细胞凋亡，但尚无关于其对肥大细胞增殖影响的报道。在此我们表明，染料木黄酮降低了肥大细胞瘤细胞系p815和RBL - 2H的活力，但对人肥大细胞系HMC - 1没有影响。我们对p815肥大细胞瘤细胞的生长抑制机制进行了进一步研究。染料木黄酮诱导G2/M期阻滞并随后导致凋亡死亡。经历凋亡的p815细胞表现出许多凋亡特征，如线粒体膜电位降低、细胞色素c释放到细胞质、凋亡诱导因子转位到细胞核、caspase - 3激活、核浓缩以及DNA片段化。染料木黄酮处理导致Bax表达增加并转位到线粒体，而Bcl - 2的表达水平保持不变。在染料木黄酮处理后的早期时间点蛋白酶体活性降低，但此后其在升高水平波动。蛋白酶体抑制剂乳胞素增强了凋亡诱导作用。综上所述，染料木黄酮诱导的p815肥大细胞瘤细胞凋亡至少部分由蛋白酶体、Bax、凋亡诱导因子和caspase介导，并通过与蛋白酶体抑制剂乳胞素共同处理而增强。
