title: Obatoclax induces Beclin 1- and ATG5-dependent apoptosis and autophagy in adenoid cystic carcinoma cells.
abstract: OBJECTIVE
  Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism.
  
  
  METHODS
  Western blot, transmission electron microscopy, and pEGFP-LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3-MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay.
  
  
  RESULTS
  We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax-induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax.
  
  
  CONCLUSIONS
  In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax-induced autophagy and apoptosis in adenoid cystic carcinoma.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: L-Z
authors.initials: LZ
authors.lastname: Liang
authors.forename: B
authors.initials: B
authors.lastname: Ma
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Liang
authors.forename: H-C
authors.initials: HC
authors.lastname: Liu
authors.forename: T-H
authors.initials: TH
authors.lastname: Zhang
authors.forename: G-S
authors.initials: GS
authors.lastname: Zheng
authors.forename: Y-X
authors.initials: YX
authors.lastname: Su
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Liao
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071187:Autophagy-Related Protein 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071186:Beclin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007211:Indoles; D011379:Prognosis; D011758:Pyrroles / Q000494:pharmacology*; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; D000071186:Beclin-1; D007211:Indoles; D011758:Pyrroles; C520962:obatoclax
keywords: ATG5; adenoid cystic carcinoma; apoptosis; autophagy; beclin 1