The inhibitory mechanism by curcumin on the Zac1-enhanced cyclin D1 expression in human keratinocytes.

BACKGROUND: ZAC, a zinc finger protein regulating cell cycle arrest and apoptosis, mRNA was found highly expressed in the hyper-proliferative epidermal compartment of psoriatic skin. On the other hand, curcumin has been tried for treatment of psoriasis partly due to its anti-proliferative property.

OBJECTIVES: Since cyclin D1 is a positive regulator for cell-cycle progression and its expression can be inhibited by curcumin, we would like to test whether the expression of cyclin D1 can be affected by Zac1. The cross-talk between curcumin and Zac1 upon the regulation of cyclin D1 expression will also be explored in the HaCaT cell line.

METHODS: Cyclin D1 promoter luciferase reporter was used to measure the transcriptional activity of Zac1 in the absence or presence of curcumin treatment for HaCaT cells. Likewise, RT-PCR, western blotting and flow cytometry were employed to evaluate the expression of Zac1, cyclin D1 and other negative regulators of S phase entry in cell-cycle.

RESULTS: Zac1 enhances the expression of cyclin D1, but curcumin decreases both the expression of Zac1 and cyclin D1. Interestingly, Zac1-induced cyclin D1 promoter activity is abolished by curcumin. Supportively, curcumin indeed exhibits an inhibitory effect to prevent cultured keratinocytes from entry into S phase in the cell cycle.

CONCLUSIONS: These findings revealed that Zac1 modulates not only cell differentiation and apoptosis but also cell proliferation. The experimental results implied that curcumin may inhibit the expression of ZAC, consequently down-regulate the cyclin D1 expression and decelerate cell-cycle progression of psoriatic keratinocytes.