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J Dermatol Sci. 2015 Sep;79(3):262-7. doi: 10.1016/j.jdermsci.2015.06.006. Epub 2015 Jun 15.

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

Author information

1
Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
2
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
3
School of Nursing, National Defense Medical Center, Taipei, Taiwan; School of Nursing, National Yang-Ming University, Taipei, Taiwan.
4
Department of Dermatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan. Electronic address: ades0431@ms38.hinet.net.

Abstract

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.

KEYWORDS:

Curcumin; Cyclin D1; Keratinocyte; Psoriasis; Zac1

PMID:
26094054
DOI:
10.1016/j.jdermsci.2015.06.006
[Indexed for MEDLINE]

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