Oridonin induces apoptosis in human oral cancer cells via phosphorylation of histone H2AX.

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Oridonin, a natural diterpenoid purified from Rabdosia rubescens, has displayed beneficial biological activities, including anti-proliferation and anti-angiogenesis effects, in various types of cancers. However, the anti-cancer potential of oridonin and its mechanism in oral cancer have never previously been studied. In this study, we assessed the role of oridonin as an inducer of apoptosis in HSC-3 and HSC-4 human oral cancer cells. Our results showed that oridonin reduces the viability of human oral cancer cells and significantly increases the expression of γH2AX, a well-known marker of DNA damage. 4',6-Diamidino-2-phenylindole (DAPI) staining and western blotting showed that oridonin causes nuclear condensation and fragmentation, and induces cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, oridonin-induced γH2AX accumulation was partially abrogated by Z-VAD, a pan-caspase inhibitor. Taken together, our results suggest that oridonin can effectively induce apoptosis by augmenting the expression of γH2AX in response to DNA damage and might be a promising anti-cancer drug candidate for the treatment of oral cancer.

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