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20S-人参皂苷Rh2通过线粒体信号通路诱导人白血病Reh细胞凋亡。

20S-Ginsenoside Rh2 induces apoptosis in human Leukaemia Reh cells through mitochondrial signaling pathways.

作者信息

Xia Ting, Wang Jian-Cheng, Xu Wei, Xu Lu-Hong, Lao Chong-Hui, Ye Qi-Xiang, Fang Jian-Pei

机构信息

Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University.

出版信息

Biol Pharm Bull. 2014;37(2):248-54. doi: 10.1248/bpb.b13-00667.

Abstract

20(S)-Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are members of the protopanaxadiol family and have been investigated for possible chemopreventive activity. This study explored the biological and apoptotic mechanisms induced by 20(S)-GRh2 in human acute leukaemia line-Reh cells. Reh cells were treated with different concentration of 20(S)-GRh2 in vitro. Cell viability was determined by Cell Counting Kit-8 and Annexin V/7-AAD assays. Mitochondrial membrane potential (MMP) was examined through JC-1 staining. Activation of caspases associated with the mitochondria-mediated apoptosis pathway was determined by Western blot. We observed that survival of Reh cells decreased after exposure to 20(S)-GRh2 in a concentration-dependent manner. Moreover, 20(S)-GRh2 can induce mitochondria depolarization of Reh cells as evident in the shift in JC-1 fluorescence from red to green. In addition, 20(S)-GRh2 induced the release of mitochondrial cytochrome c and activation of caspase-9 and caspase-3 in Reh cells. These results indicate that 20(S)-GRh2 could induce apoptosis through the mitochondrial pathway, demonstrating its potential as a chemotherapeutic agent for leukaemia therapy.

摘要

20(S)-人参皂苷Rh2(GRh2)和人参皂苷Rg3(GRg3)属于原人参二醇家族成员,人们已对其潜在的化学预防活性进行了研究。本研究探讨了20(S)-GRh2对人急性白血病细胞系-Reh细胞诱导的生物学及凋亡机制。体外使用不同浓度的20(S)-GRh2处理Reh细胞。通过细胞计数试剂盒-8及膜联蛋白V/7-氨基放线菌素D检测法测定细胞活力。通过JC-1染色检测线粒体膜电位(MMP)。采用蛋白质免疫印迹法测定与线粒体介导的凋亡途径相关的半胱天冬酶的激活情况。我们观察到,暴露于20(S)-GRh2后,Reh细胞的存活率呈浓度依赖性下降。此外,20(S)-GRh2可诱导Reh细胞的线粒体去极化,这在JC-1荧光从红色转变为绿色中明显可见。另外,20(S)-GRh2可诱导Reh细胞线粒体细胞色素c的释放以及半胱天冬酶-9和半胱天冬酶-3的激活。这些结果表明,20(S)-GRh2可通过线粒体途径诱导凋亡,证明其作为白血病治疗化疗药物的潜力。

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