Protective effect of Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract against cisplatin-induced apoptosis of human HaCaT keratinocytes: Involvement of NF-kappa B- and Bcl-2-controlled mitochondrial signaling

Phytomedicine. 2015 Jun 1;22(6):679-88. doi: 10.1016/j.phymed.2015.04.003. Epub 2015 May 13.

Abstract

Background: Oral mucositis is a common adverse effect of antineoplastic chemotherapy limiting sufficient dose of chemoregimen. Numerous attempts to mitigate chemotherapy-induced oral mucositis have failed to identify an appropriate treatment.

Hypothesis: We hypothesize that Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract (Aa-EE) would mitigate cisplatin-induced cytotoxicity to oral mucosal epithelial cells.

Study design: In vitro experimental study.

Methods: Cell viability and wound healing assay were performed. Apoptosis, mitochondrial membrane potential (MMP) change, and changes in apoptosis-related signaling were demonstrated in human primary keratinocyte (HaCaT).

Results: Cisplatin inhibited HaCaT cell proliferation and migration. Aa-EE protected against these effects. Cisplatin treatment of HaCaT cells caused apoptosis and changes in MMP. Aa-EE inhibited cisplatin-induced apoptosis, and stabilized the cisplatin-induced loss of MMP. Western blots revealed that Aa-EE reduced the expression of cytochrome c and cleaved caspase-3 and inhibited nuclear translocation of nuclear factor-kappa B (NF-κB), compared with the levels observed after cisplatin treatment, whereas Bcl-2 expression was increased by Aa-EE.

Conclusion: Collectively, our results suggest that Aa-EE protects HaCaT cells by inhibiting cisplatin-induced mitochondrial damage associated with Bcl-2 activity and by inhibiting nuclear translocation of NF-κB.

Keywords: Apoptosis; Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract; Bcl-2; Cisplatin-induced mucositis; Eupatilin; Nuclear factor-kappa B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Artemisia / chemistry*
  • Cell Line
  • Cisplatin / adverse effects
  • Flavonoids / pharmacology
  • Humans
  • Keratinocytes / drug effects*
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism*
  • NF-kappa B / metabolism*
  • Plant Components, Aerial / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Signal Transduction

Substances

  • BCL2 protein, human
  • Flavonoids
  • NF-kappa B
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • eupatilin
  • Cisplatin