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

Int Immunopharmacol. 2012 Jun;13(2):170-4. doi: 10.1016/j.intimp.2012.03.025. Epub 2012 Apr 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Keratinocytes / cytology*
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • NF-kappa B / metabolism
  • Psoriasis / drug therapy
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / administration & dosage
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation / drug effects


  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Curcumin