YM-155 potentiates the effect of ABT-737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context

• Published in: Molecular cancer therapeutics Vol. 12; no. 3; pp. 326 - 338
• Main Authors: Jane, Esther P, Premkumar, Daniel R, DiDomenico, Joseph D, Hu, Bo, Cheng, Shi-Yuan, Pollack, Ian F
• Format: Journal Article
• Language: English
• Published: United States 01.03.2013
• Subjects: Apoptosis - drug effects; bcl-X Protein - antagonists & inhibitors; bcl-X Protein - genetics; bcl-X Protein - metabolism; Biphenyl Compounds - pharmacology; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Cell Line, Tumor; Down-Regulation; Drug Resistance, Neoplasm - genetics; Gene Expression Regulation, Neoplastic - drug effects; Glioma - drug therapy; Glioma - genetics; Glioma - metabolism; Humans; Imidazoles - pharmacology; Inhibitor of Apoptosis Proteins - antagonists & inhibitors; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Myeloid Cell Leukemia Sequence 1 Protein; Naphthoquinones - pharmacology; Nitrophenols - pharmacology; Piperazines - pharmacology; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction; Sulfonamides - pharmacology

Antiapoptotic proteins are commonly overexpressed in gliomas, contributing to therapeutic resistance. We recently reported that clinically achievable concentrations of the Bcl-2/Bcl-xL inhibitor ABT-737 failed to induce apoptosis in glioma cells, with persistent expression of survivin and Mcl-1. To...