Lung Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Cancer, including details on symptoms, smoking, genetics, treatment, causes. | ||||||||
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Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells.Ghosh AK, Steele R, Ryerse J, Ray RB Department of Pathology and Cancer Center, Saint Louis University, St. Louis, Missouri 63104, USA. Lung cancer is the leading cause of cancer death among both men and women. Only approximately 15% of people diagnosed with non-small cell lung cancer (NSCLC) survive this disease beyond 5 years. Thus, novel therapeutic strategies are urgently needed to improve the clinical management of this devastating disease. We have previously shown the antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of non-small cell lung tumor growth. We have observed that exogenous expression of MBP-1 in NSCLC cells (H1299) induces massive cell death. To determine the gene therapeutic potential of MBP-1, replication-deficient recombinant adenovirus expressing MBP-1 was given intratumorally in human lung cancer xenografts in nude mice. Our results showed a significant regression of lung tumor growth and prolonged survival on treatment with MBP-1 compared with the control groups (saline or dl312). Subsequently, the mechanism of MBP-1-mediated H1299 cell death was investigated. Our results suggested that MBP-1 induced poly(ADP-ribose) polymerase cleavage in H1299 cells; however, treatment with pan-caspase inhibitor did not protect against MBP-1-induced cell death. Cells transduced with MBP-1 displayed early plasma membrane permeability, mitochondrial damage without cytochrome c release, and extensive cytoplasmic vacuolation, yielding a morphotype that is typical of necrosis. Taken together, this study suggests that MBP-1 expression induces a novel form of necrosis-like cell death and MBP-1 could be a potential gene therapeutic candidate against non-small cell lung tumor growth. Published 20 December 2006 in Cancer Res, 66(24): 11907-12.
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