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Molecular mechanisms of ginsenoside Rp1-mediated growth arrest and apoptosis.

机译:人参皂苷Rp1介导的生长停滞和凋亡的分子机制。

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Ginsenoside Rp1, a semi-synthesized ginseng saponin, was shown to have chemopreventive action and anti-metastatic potential. However, the molecular mechanisms of Rp1 on cell growth and death are not fully understood. In this study, the antiproliferative effect of Rp1 on HeLa cells in vitro was investigated. Treatment with Rp1 at 40 microM inhibited the proliferation and partial accumulation of cells at the G1 phase. Rp1-mediated G1 arrest was accompanied by decreased expression of cyclin D1, E, and A and increased expression of p21 without any significant change in p53 or phospho-p53 (Ser15). On the other hand, prolonged incubation with Rp1 at 40 microM caused apoptosis and activation of caspase-3, -8, and -9. The participation of these three caspases in apoptosis was more clearly shown in experiments using inhibitors, which markedly prevented Rp1-induced apoptosis in the case of each caspase. Cleavage of the polyADP-ribose polymerase, often used as an apoptotic marker, was also found in Rp1-induced apoptosis. Among Bcl-2 family proteins (Bad, Bax, Bid, Bcl-2), Bax and Bid were activated by Rp1 treatment, which resulted in the release of cytochrome c from mitochondria, following activation of caspase-9. These observations indicate that multiple cell cycle regulatory proteins and apoptosis-inducing proteins are regulated by Rp1 and contribute to Rp1-induced growth arrest and apoptosis.
机译:人参皂苷Rp1是一种半合成人参皂苷,具有化学预防作用和抗转移潜力。但是,Rp1对细胞生长和死亡的分子机制尚未完全了解。在这项研究中,研究了Rp1对HeLa细胞的体外抗增殖作用。用40 microM的Rp1处理可抑制G1期细胞的增殖和部分积累。 Rp1介导的G1阻滞伴随着细胞周期蛋白D1,E和A的表达降低以及p21的表达增加,而p53或磷酸化p53(Ser15)却没有任何显着变化。另一方面,与Rp1在40 microM下长时间孵育会导致凋亡和caspase-3,-8和-9的激活。在使用抑制剂的实验中,这三个半胱天冬酶参与了凋亡,这在每种胱天蛋白酶的情况下均能明显阻止Rp1诱导的凋亡。通常在Rp1诱导的凋亡中也发现了通常用作凋亡标记的polyADP-核糖聚合酶的切割。在Bcl-2家族蛋白(Bad,Bax,Bid,Bcl-2)中,Bax和Bid通过Rp1处理激活,导致caspase-9激活后从线粒体释放细胞色素c。这些观察表明,多种细胞周期调节蛋白和诱导凋亡的蛋白受Rp1调节,并有助于Rp1诱导的生长停滞和凋亡。

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