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.