Xia Mingyu, Wang Dong, Wang Minwei, Tashiro Shin-Ichi, Onodera Satoshi, Minami Mutsuhiko, Ikejima Takashi
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
J Pharmacol Sci. 2004 Jun;95(2):273-83. doi: 10.1254/jphs.fpj03102x.
Dracorhodin perchlorate inhibited proliferation of several tumor cell lines. The drug induced oligonucleosomal fragmentation of DNA in HeLa cells and increased caspase-3, -8, -9 activities followed by the degradation of caspase-3 substrates, inhibitor of caspase-dependent DNase, and poly-(ADP-ribose) polymerase. It also increased caspase-1 activity and a caspase-1 inhibitor, Ac-YVAD-cmk, and a caspase-10 inhibitor z-AEVD-fmk, also reduced dracorhodin-perchlorate-induced HeLa cell death. Dracorhodin perchlorate decreased the expression of anti-apoptotic mitochondrial protein, Bcl-X(L), but not Bcl-2; and it increased the expression of pro-apoptotic protein, Bax. Dracorhodin perchlorate induced a sustained generation of reactive oxygen species (ROS) in HeLa cells; caspase-1 inhibitor, Ac-YVAD-cmk, and caspase-3 inhibitor, z-DEVD-fmk, attenuated the generation of ROS. Taken together, our results indicate that dracorhodin perchlorate alters the intracellular redox status, changed the balance of Bcl-X(L) and Bax protein expression, and induces apoptosis through caspase pathways in HeLa cells.
高氯酸血根碱抑制多种肿瘤细胞系的增殖。该药物在HeLa细胞中诱导DNA的寡核小体片段化，并增加caspase-3、-8、-9的活性，随后caspase-3底物、caspase依赖性脱氧核糖核酸酶抑制剂和聚（ADP-核糖）聚合酶发生降解。它还增加caspase-1活性，并且一种caspase-1抑制剂Ac-YVAD-cmk和一种caspase-10抑制剂z-AEVD-fmk也能减少高氯酸血根碱诱导的HeLa细胞死亡。高氯酸血根碱降低抗凋亡线粒体蛋白Bcl-X(L)的表达，但不影响Bcl-2的表达；并且它增加促凋亡蛋白Bax的表达。高氯酸血根碱在HeLa细胞中诱导活性氧（ROS）的持续产生；caspase-1抑制剂Ac-YVAD-cmk和caspase-3抑制剂z-DEVD-fmk减弱了ROS的产生。综上所述，我们的结果表明，高氯酸血根碱改变细胞内氧化还原状态，改变Bcl-X(L)和Bax蛋白表达的平衡，并通过caspase途径在HeLa细胞中诱导凋亡。
