Cytoprotective responses in HaCaT keratinocytes exposed to high doses of curcumin

Ditte M. S. Lundvig, Sebastiaan W. C. Pennings, Katrien M. Brouwer, Matilda Mtaya-Mlangwa, Emeria Mugonzibwa, Anne Marie Kuijpers-Jagtman, Frank A. D. T. G. Wagener, Johannes W. Von den Hoff*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

Abstract

Wound healing is a complex process that involves the well-coordinated interactions of different cell types. Topical application of high doses of curcumin, a plant-derived polyphenol, enhances both normal and diabetic cutaneous wound healing in rodents. For optimal tissue repair interactions between epidermal keratinocytes and dermal fibroblasts are essential. We previously demonstrated that curcumin increased reactive oxygen species (ROS) formation and apoptosis in dermal fibroblasts, which could be prevented by pre-induction of the cytoprotective enzyme heme oxygenase (HO)-1. To better understand the effects of curcumin on wound repair, we now assessed the effects of high doses of curcumin on the survival of HaCaT keratinocytes and the role of the HO system. We exposed HaCaT keratinocytes to curcumin in the presence or absence of the HO-1 inducers heme (FePP) and cobalt protoporphyrin (CoPP). We then assessed cell survival, ROS formation, and caspase activation. Curcumin induced caspase-dependent apoptosis in HaCaT keratinocytes via a ROS-dependent mechanism. Both FePP and CoPP induced HO-1 expression, but only FePP protected against curcumin-induced ROS formation and caspase-mediated apoptosis. In the presence of curcumin, FePP but not CoPP induced the expression of the iron scavenger ferritin. Together, our data show that the induction of ferritin, but not HO, protects HaCaT keratinocytes against cytotoxic doses of curcumin. The differential response of fibroblasts and keratinocytes to high curcumin doses may provide the basis for improving curcumin-based wound healing therapies. (C) 2015 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)298-307
Number of pages10
JournalExperimental Cell Research
Volume336
Issue number2
DOIs
Publication statusPublished - 15-Aug-2015
Externally publishedYes

Keywords

  • Keratinocytes
  • Curcumin
  • Heme oxygenase-1
  • Ferritin
  • Cytoprotection
  • ROS
  • MICROSOMAL HEME OXYGENASE
  • OXIDATIVE STRESS
  • APOPTOSIS
  • IRON
  • FIBROBLASTS
  • ANTIOXIDANT
  • EXPRESSION
  • CELLS
  • METALLOPORPHYRINS
  • SUPPRESSION

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