Curcumin induces apoptosis in tumor necrosis factor-alpha-treated HaCaT cells

Psoriasis is a benign, chronic skin disease characterized by keratinocyte hyperproliferation and abnormal differentiation. Curcumin, a selective phosphorylase kinase inhibitor, is a natural phytochemical present in turmeric. Curcumin has been confirmed to have anti-inflammatory properties as well as the ability to inhibit proliferation and decrease the expression of pro-inflammatory cytokines in psoriatic keratinocytes. However. the pro-apoptotic effect of curcumin in keratinocytes remains unclear. In the present study, we investigated the effect of curcumin on apoptosis induction in TNF-alpha-treated HaCaT cells. These results show that curcumin exhibited a significant pro-apoptotic effect on HaCaT cells only in the presence of TNF-alpha and/or TRAIL The pro-apoptotic effect of curcumin resulted from the increased expression of TRAIL-R1/R2 and the decreased expression of anti-apoptotic proteins. Our results indicate that both curcumin and TNF-alpha upregulated the expression of TRAIL-R1/R2. In addition, the expression of anti-apoptotic proteins (IAP1, IAP2, Bcl-X-L) was upregulated by INF-alpha but suppressed by curcumin in HaCaT cells. Because these proteins are regulated by NF-kappa B, we examined the role of curcumin in NF-kappa B activation. As expected, curcumin inhibited TNF-alpha-induced activation of NF-kappa B, including NF-kappa B-P65. Curcumin also inhibited the TNF-alpha-induced production of IL-6/1L8 in HaCaT cells. These results imply that curcumin-induced apoptosis of HaCaT cells only occurs when TNF-alpha or/and TRAIL are present. Therefore, we believe that curcumin is able to reverse the anti-apoptotic function of TNF-alpha in HaCaT cells and thus expect curcumin to be successful in the treatment of psoriasis. (C) 2012 Elsevier B.V. All rights reserved.