title: 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.
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.
  
  
  OBJECTIVE
  We hypothesize that Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract (Aa-EE) would mitigate cisplatin-induced cytotoxicity to oral mucosal epithelial cells.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea; Center for Cell Death Regulating Biodrugs, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea; Center for Cell Death Regulating Biodrugs, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Yeon Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea; Center for Cell Death Regulating Biodrugs, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Haeng Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea; Center for Cell Death Regulating Biodrugs, School of Medicine, Ajou University, Suwon, Republic of Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Rajavithi Hospital, Bangkok, Thailand.
authors.forename: Tatsanachat
authors.initials: T
authors.lastname: Jittreetat
authors.affiliation: Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea; Center for Cell Death Regulating Biodrugs, School of Medicine, Ajou University, Suwon, Republic of Korea. Electronic address: ostium@ajou.ac.kr.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019306:Artemisia / Q000737:chemistry*; D002460:Cell Line; D002945:Cisplatin / Q000009:adverse effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C000595707:BCL2 protein, human; D005419:Flavonoids; D016328:NF-kappa B; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; C045325:eupatilin; D002945:Cisplatin
keywords: Apoptosis; Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract; Bcl-2; Cisplatin-induced mucositis; Eupatilin; Nuclear factor-kappa B