title: Transcriptional regulation of Mcl-1 plays an important role of cellular protective effector of vincristine-triggered autophagy in oral cancer cells.
abstract: OBJECTIVE
  The autophagy-associated release of HMGB1 (high-mobility group box 1) has been reported that protect cancer cells from numerous chemotherapeutics. However, the related molecular mechanism involved in the protection of oral cancer cells remains unclear.
  
  
  METHODS
  In this study, we determined that HMGB1 released by oral cancer cells protected the cells against apoptosis caused by vincristine by upregulating the transcription of Mcl-1.
  
  
  RESULTS
  Extracellular HMGB1 seems to be required for the autophagy-mediated inhibition of apoptosis because the effect of autophagy protection was abolished by HMGB1 knockdown. Vincristine treatment increased the expression of Mcl-1 mRNA, but decreased the Mcl-1 protein expression. HMGB1 expression inhibited blocked the Mcl-1 transcription increase and reduced Mcl-1 expression, demonstrate that HMGB1 is required for the upregulation of Mcl-1 transcriptional, and thereby maintaining Mcl-1 protein expression levels is required for the survival of oral cancer cells by vincristine.
  
  
  CONCLUSIONS
  Collectively, this study suggested that the HMGB1-mediated Mcl-1 transcription upregulation is a key mechanism by which autophagy protects oral cancer cells against vincristine-induced apoptosis.
authors.affiliation: Changhua Christian Hospital, Cancer Research Center , Changhua 500, Taiwan , ROC.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chiou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000235:genetics*; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D024243:HMGB1 Protein; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D014750:Vincristine
keywords: Mcl-1; apoptosis; autophagy; high-mobility group box 1; vincristine