MDA-7 regulates cell growth and radiosensitivity in vitro of primary (Non-Established) human glioma cells

• DOI: 10.4161/cbt.3.8.968
• Publication Date: 2010-07-16T16:42:04Z
• Authors: Adly Yacoub; Clint Mitchell; Young Hong; Rahul V. Gopalkri...; Zhao-Zhong Su; Pankaj Gupta; Moira Sauane; Irina V. Lebedeva; David T. Curiel; Parameshwar J. Ma...; Myrna R. Rosenfeld; William C. Broaddus; C. Davis James; Steven Grant; Paul B. Fisher; Paul Dent
• Keywords: Clonogenic assay; Viability assay; Growth inhibition

We examined the impact of purified bacterially synthesized GST-MDA-7 (IL-24) and ionizing radiation on proliferation survival non-established human glioblastoma multiforme (GBM) cells. Glioma cell types expressing mutated PTEN p53 molecules, activated ERBB1VIII, over-expressing wild type ERBB1 or without receptor over-expression were selected. In MTT assays, caused a dose-dependent reduction in glioma cells; however only at higher concentrations did reduce viability. The anti-proliferative cytotoxic effects enhanced by greater than additive fashion that correlated with JNK1/2/3 activation. growth enhancement killing combination blocked an ROS scavenger, N-acetyl cysteine (NAC), inhibitor SP600125, pan-caspase (zVAD) caspase 9 (LEHD), but not 8 (IETD). Low either reduced clonogenic survival, colony formation ability was significantly further decreased when two treatments combined, which also inhibition function. general agreement activation intrinsic pathway, death BCL-XL expression increased levels pro-apoptotic proteins BAD BAX. Inhibition after treatment blunted neither nor BAX, block 3 cleavage, ERK1/2 activity. contrast, incubation NAC killing, increases BAX expression. These findings argue is primary event loss activity are secondary caspase-dependent processes. This data argues induces parallel pathways via ROS-dependent -independent mechanisms. Infection astrocytes recombinant adenovirus to express MDA-7, Ad.mda-7, infection Ad.cmv Ad.mda-7SP- lacking MDA-7 secretion, resulted suppression GBM soft agar overlay effect radiation. Collectively, our demonstrate reduces enhances radiosensitivity cells vitro, grown dimensions, sensitization occurs independently basal EGFR / AKT functions p53.