Anticancer activity of herbal formula Jisilhaebaekgyeji-Tang against human breast cancer cells and its mechanism

Abstract

Background Jisilhaebaekgyeji-Tang (JHG, Zhishi Xiebai Guizhi Tang) is a famous traditional herbal medicine described in the Geumgweyoryak (Jin Gui Yao Lue), an ancient Chinese medical text. JHG is composed of five medicinal herbs and is used to treat thoracic obstructions in China, Japan, and Korea. Although it has been reported the inhibitory effect of JHG against skin and lung cancers, there is a lack of reliable scientific evidence supporting its efficacy. Objective In the present study, we investigated the effects of JHG on human breast cancer cell lines and explored the underlying mechanisms. The anticancer effects of the JHG were evaluated in human breast cancer cell lines and human umbilical vein endothelial cells (HUVECs). Results An ethanol extract of JHG suppressed the growth of cells representing four subtypes of human breast cancer. In particular, JHG showed the greatest inhibitory effect against MCF-7 cells and was found to significantly reduce the mitochondrial membrane potential. Furthermore, the extract dose-dependently inhibited the expression of BCL-2, MCL-1, survivin, and procaspases-9 and -7 and induced nuclear condensation and fragmentation. In MCF-7 cells, the JHG extract inhibited the phosphorylation of the estrogen receptor alpha (ER alpha) and the activation of the mTOR and ERK pathways but enhanced the phosphorylation of p38 mitogen-activated protein kinase. In addition, the extract attenuated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor signaling pathway under hypoxia-mimicking conditions and inhibited the metastatic ability of MCF-7 cells, including their migration and invasion activities, and the angiogenic properties of HUVECs. Conclusion The results suggest that the JHG extract exerts potent anticancer effects and that these effects may be due to the inhibition of ER alpha and the induction of intrinsic pathway-mediated apoptosis in MCF-7 cells.