Curcumin provides potential protection against the activation of hypoxia and prolyl 4-hydroxylase inhibitors on prostate-specific antigen expression in human prostate carcinoma cells

Scope: Prostate‐specific antigen (PSA) is a well‐known marker for diagnosing and monitoring prostate cancer. Curcumin, a yellow curry pigment, has been reported to enhance androgen receptor (AR) degradation. We examined the effects of curcumin on increasing PSA expression by hypoxia and prolyl hydroxylase inhibitors, L ‐mimosine and dimethyloxalylglycine (DMOG), in human prostate carcinoma LNCaP cells. Methods and results: The ³H‐thymidine incorporation assay revealed that either L ‐mimosine or DMOG treatments attenuated cell proliferation. Immunoblot and enzyme‐linked immunosorbent assays (ELISA) indicated that both L ‐mimosine and DMOG have an effect similar to hypoxia, which stabilized hypoxia‐inducible factor‐1α (HIF‐1α) and induced PSA gene expression. The results of the immunoblot and transient gene expression assays indicated that induction of the PSA expression by hypoxia is both HIF‐1α‐ and AR‐dependent. Immunoblot assays revealed that a curcumin treatment (10 μM) decreased the protein abundance of AR but did not significantly affect the protein levels of HIF‐1α and vascular endothelial growth factor, which were induced by hypoxia. ELISA and transient gene expression assays indicated that curcumin blocked the activation of L ‐mimosine or DMOG treatment on PSA expression. Conclusions: These results indicate that curcumin blocked the enhanced effect of PSA expression by L ‐mimosine and DMOG that induce hypoxia condition.