title: Kaempferol suppresses cisplatin-induced apoptosis via inductions of heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit in HEI-OC1 cell.
abstract: OBJECTIVE
  The present study was undertaken to elucidate the chemoprotective mechanism of kaempferol, which possesses anti-oxidative and anti-apoptotic properties.
  
  
  METHODS
  House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with kaempferol in the presence or absence of cisplatin. Cisplatin-induced oxidative stress was assessed by analysis of Comet assay, DNA-laddering assay and activation of caspases. Heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK) pathway and nuclear factor-E2-related factor 2 (Nrf2) were measured by Western blot analysis. Transfection of small interfering RNAs (siRNA), glutathione (GSH) assay and RT-PCR were performed in this study.
  
  
  RESULTS
  Kaempferol protected cells against cisplatin-induced apoptosis in a dose-dependent manner in HEI-OC1 cells. Kaempferol-induced HO-1 expression protected against cell death though the c-Jun N-terminal kinase (JNK) pathway and by the aid of Nrf2 translocation. Kaempferol increased the cellular level of GSH and the expression of GCLC time-dependently. siRNA GCLC blocked the increase of GSH level by kaempferol and the protective effect of kaempferol against cisplatin-induced cell death.
  
  
  CONCLUSIONS
  The expression of HO-1 by kaempferol inhibits cisplatin-induced apoptosis in HEI-OC1 cells, and the mechanism of protective effect is also associated with its inductive effect of GCLC expression.
authors: Vestibulocochlear Research Center and Department of Biochemistry, School of Medicine, Wonkwang University, Chonbuk, 570-749, Republic of Korea.
authors: Shang Shang
authors: SS
authors: Gao
authors: Byung-Min
authors: BM
authors: Choi
authors: Xiao Yan
authors: XY
authors: Chen
authors: Ri Zhe
authors: RZ
authors: Zhu
authors: Youngho
authors: Y
authors: Kim
authors: HongSeob
authors: H
authors: So
authors: Raekil
authors: R
authors: Park
authors: Meesook
authors: M
authors: Sung
authors: Bok-Ryang
authors: BR
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020134:Catalytic Domain / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D044949:Kaempferols / Q000502:physiology*; D051379:Mice; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D044949:Kaempferols; C006552:kaempferol; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase; D002945:Cisplatin