title: Curcumin induces apoptosis in tumor necrosis factor-alpha-treated HaCaT cells.
abstract: 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-α-treated HaCaT cells. These results show that curcumin exhibited a significant pro-apoptotic effect on HaCaT cells only in the presence of TNF-α 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-α up-regulated the expression of TRAIL-R1/R2. In addition, the expression of anti-apoptotic proteins (IAP1, IAP2, Bcl-X(L)) was up-regulated by TNF-α but suppressed by curcumin in HaCaT cells. Because these proteins are regulated by NF-κB, we examined the role of curcumin in NF-κB activation. As expected, curcumin inhibited TNF-α-induced activation of NF-κB, including NF-κB-P65. Curcumin also inhibited the TNF-α-induced production of IL-6/IL-8 in HaCaT cells. These results imply that curcumin-induced apoptosis of HaCaT cells only occurs when TNF-α or/and TRAIL are present. Therefore, we believe that curcumin is able to reverse the anti-apoptotic function of TNF-α in HaCaT cells and thus expect curcumin to be successful in the treatment of psoriasis.
authors.affiliation: Department of Pharmacy, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Jinzhao
authors.initials: J
authors.lastname: Han
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Quangang
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jinhong
authors.initials: J
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D003474:Curcumin