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

BackgroundOral 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.HypothesisWe hypothesize that Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract (Aa-EE) would mitigate cisplatin-induced cytotoxicity to oral mucosal epithelial cells.Study designIn vitro experimental study.MethodsCell 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).ResultsCisplatin 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.ConclusionCollectively, 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.

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