title: BV6, an IAP antagonist, activates apoptosis and enhances radiosensitization of non-small cell lung carcinoma in vitro.
abstract: BACKGROUND
  Defects in the apoptosis pathway limit the effectiveness of radiation in non-small cell lung cancer (NSCLC) therapy. BV6 is an antagonist of cIAP1 and XIAP, members of the inhibitors of apoptosis (IAP) family. We investigated the potential of BV6 to sensitize NSCLC cell lines to radiation.
  
  
  METHODS
  HCC193 and H460 lung cancer cell lines were treated with BV6 to investigate the effects of drug administration on cell proliferation, apoptosis, inhibition of XIAP and cIAP1, and radiosensitivity. Subsequent immunoblotting and Hoechst staining were used to determine the role of apoptosis in radiosensitization. Finally, the pathway of apoptosis was characterized by Western blot analysis for cleaved caspase-8 and cleaved caspase-9 and enzyme-linked immunosorbent assays for TNF-α.
  
  
  RESULTS
  HCC193 was found to be more sensitive than H460 to BV6-induced apoptosis in a concentration-dependent and time-dependent manner. BV6 significantly sensitized both cell lines to radiation (HCC193-DER = 1.38, p < 0.05 at 1 μM BV6; H460-DER = 1.42, p < 0.05 at 5 μM BV6), but a higher concentration of and longer incubation time with BV6 was necessary for H460 cells. The BV6-induced radiosensitization of HCC193 favored the extrinsic pathway of apoptosis, whereas that of H460 favored the intrinsic pathway.
  
  
  CONCLUSIONS
  BV6, an IAP antagonist, significantly enhanced the radiosensitization of HCC193 and H460 cells in vitro. More research is warranted to test the mechanism of action of BV6 and to assess its potential in vivo and in the clinical setting.
authors.affiliation: Department of Radiation Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Giacalone
authors.forename: Artour
authors.initials: A
authors.lastname: Torossian
authors.forename: Yunguang
authors.initials: Y
authors.lastname: Sun
authors.forename: Kathy
authors.initials: K
authors.lastname: Niu
authors.forename: Opal
authors.initials: O
authors.lastname: Lin-Tsai
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D002588:Cesium Radioisotopes; D059248:Chemoradiotherapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002588:Cesium Radioisotopes; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D011838:Radiation-Sensitizing Agents; D014409:Tumor Necrosis Factor-alpha