Oridonin Induces Apoptosis, Inhibits Migration and Invasion on Highly-Metastatic Human Breast Cancer Cells

American Journal of Chinese Medicine - Tập 41 Số 01 - Trang 177-196 - 2013
Shengpeng Wang1,2, Zhangfeng Zhong1,2, Jian‐Bo Wan1,2, Wen Siang Tan1,2, Guosheng Wu1,2, Meiwan Chen1,2, Yitao Wang1,2
1Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
2State Key Laboratory of Quality Research in Chinese Medicine, (University of Macau) Macau SAR 999078, China

Tóm tắt

Oridonin, a natural tetracycline diterpenoid isolated from Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide variety of tumors. However, its effect on highly metastatic breast cancer cells has not been addressed. In this study, we investigated the effects of oridonin on growth, migration and invasion of highly-metastatic human breast cancer cells. Our results showed that oridonin induced potent growth inhibition on human breast cancer cells MCF-7 and MDA-MB-231 in a time- and dose-dependent manner. According to the flow cytometric analysis, oridonin suppressed MCF-7 cell growth by cell cycle arrest at the G2/M phase and caused accumulation of MDA-MB-231 cells in the Sub-G1 phase. The induced apoptotic effect of oridonin was further confirmed by a morphologic characteristics assay and TUNEL assay. Oridonin triggered the reduction of Bcl-2/Bax ratio, caspase-8, NF-κB (p65), IKKα, IKKβ, phospho-mTOR, and increased expression level of cleaved PARP, Fas and PPARγ in a time-dependent manner. Immunofluorescent analysis showed that γH2AX-containing nuclear foci were significant in oridonin-treated MDA-MB-231 cells. Meanwhile, oridonin significantly suppressed MDA-MB-231 cell migration and invasion, decreased MMP-2/MMP-9 activation and inhibited the expression of Integrin β1 and FAK. In conclusion, oridonin inhibited the growth and induced apoptosis in breast cancer cells, which might be related to DNA damage and activation of intrinsic or extrinsic apoptotic pathways. Moreover, oridonin also inhibited tumor invasion and metastasis in vitro possibly via decreasing the expression of MMPs and regulating the Integrin β1/FAK pathway in MDA-MB-231 cells.

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Thông tin xuất bản

American Journal of Chinese Medicine

Tập 41 Số 01

177-196

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