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异硫氰酸酯萝卜硫素通过激活半胱天冬酶-3诱导人宫颈癌HeLa细胞和肝癌HepG2细胞凋亡。

Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3.

作者信息

Park Soung Young, Kim Gi Young, Bae Song-Ja, Yoo Young Hyun, Choi Yung Hyun

机构信息

Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, South Korea.

出版信息

Oncol Rep. 2007 Jul;18(1):181-7.

PMID:17549366
Abstract

Sulforaphane (SFN) is an isothiocyanate that is found in abundant quantities in many cruciferous vegetables including broccoli and cauliflower. Its inhibitory effects on tumor cell growth in vitro and in vivo, which is dependent on the direct effect on cancer cells, has attracted considerable attention. This study examined the effects of SFN on the growth of human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells. The results showed that SFN inhibits the viability of both HeLa and HepG2 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies and the accumulation of the sub-G1 phase. RT-PCR and immunoblotting showed that treating the cells with SFN caused the down-regulation of anti-apoptotic Bcl-2 and Bcl-XL, and the up-regulation of pro-apoptotic Bax expression. SFN-induced apoptosis was associated with the proteolytic activation of caspase-3, and the degradation/cleavage of poly (ADP-ribose) polymerase and the beta-catenin protein. z-DEVD-fmk, a caspase-3 specific inhibitor, blocked the activation of caspase-3 and increased the survival of the SFN-treated HeLa and HepG3 cells, suggesting that caspase-3 activation is essential for SFN-induced apoptosis.

摘要

萝卜硫素(SFN)是一种异硫氰酸盐,在包括西兰花和花椰菜在内的许多十字花科蔬菜中含量丰富。它在体外和体内对肿瘤细胞生长的抑制作用,这种作用依赖于对癌细胞的直接作用,已引起了相当大的关注。本研究检测了萝卜硫素对人宫颈癌HeLa细胞和肝癌HepG2细胞生长的影响。结果表明,萝卜硫素通过诱导凋亡抑制HeLa细胞和HepG2细胞的活力,凋亡小体的形成和亚G1期的积累证明了这一点。逆转录聚合酶链反应(RT-PCR)和免疫印迹显示,用萝卜硫素处理细胞导致抗凋亡蛋白Bcl-2和Bcl-XL的下调,以及促凋亡蛋白Bax表达的上调。萝卜硫素诱导的凋亡与半胱天冬酶-3的蛋白水解激活、聚(ADP-核糖)聚合酶和β-连环蛋白的降解/切割有关。z-DEVD-fmk,一种半胱天冬酶-3特异性抑制剂,阻断了半胱天冬酶-3的激活,并提高了经萝卜硫素处理的HeLa细胞和HepG3细胞的存活率,表明半胱天冬酶-3的激活对萝卜硫素诱导的凋亡至关重要。

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