Institute of Chinese Medical Sciences, University of Macau, Av. Padre Toma's Pereira S.J., Taipa, Macau, 999078, China.
Eur J Pharmacol. 2011 Sep 30;667(1-3):50-5. doi: 10.1016/j.ejphar.2011.03.041. Epub 2011 Apr 9.
Traditional medicinal herbs are an untapped source of potential pharmaceutical compounds. This study aims to determine whether the proliferation of breast cancer cell lines could be inhibited by germacrone, a natural product isolated from Rhizoma curcuma. Germacrone treatment significantly inhibited cell proliferation, increased lactate dehydrogenase (LDH) release, and induced mitochondrial membrane potential (ΔΨm) depolarization in both MCF-7 and MDA-MB-231 cells in a dose-dependent manner. Germacrone induced MDA-MB-231 and MCF-7 cell cycle arrest at the G0/G1 and G2/M phases respectively and induced MDA-MB-231 cell apoptosis. Furthermore, germacrone treatment significantly increased Bok expression and cytochrome c release from mitochondria without affecting Bcl-2, Bcl-xL, Bax, and Bim protein expressions. In addition, germacrone treatment induced caspase-3, 7, 9, PARP cleavage. We concluded that germacrone inhibited the proliferation of breast cancer cell lines by inducing cell cycle arrest and apoptosis through mitochondria-mediated caspase pathway. These results might provide some molecular basis for the anti-tumor activity of Rhizoma curcuma.
传统草药是潜在药物化合物的未开发来源。本研究旨在确定倍半萜烯是否可以抑制乳腺癌细胞系的增殖，倍半萜烯是从姜黄根茎中分离得到的天然产物。倍半萜烯处理以剂量依赖性方式显著抑制 MCF-7 和 MDA-MB-231 细胞的增殖，增加乳酸脱氢酶（LDH）释放，并诱导线粒体膜电位（ΔΨm）去极化。倍半萜烯诱导 MDA-MB-231 和 MCF-7 细胞周期分别在 G0/G1 和 G2/M 期停滞，并诱导 MDA-MB-231 细胞凋亡。此外，倍半萜烯处理显著增加 Bok 表达和线粒体细胞色素 c 释放，而不影响 Bcl-2、Bcl-xL、Bax 和 Bim 蛋白表达。此外，倍半萜烯处理诱导 caspase-3、7、9、PARP 切割。我们得出结论，倍半萜烯通过线粒体介导的半胱天冬酶途径诱导细胞周期停滞和细胞凋亡来抑制乳腺癌细胞系的增殖。这些结果可能为姜黄的抗肿瘤活性提供一些分子基础。
