Regulating apoptosis in TRAIL-resistant cancer cells, while protecting normal, non-cancerous cells

摘要

Provided are compositions and methods for controlling, modulating or regulating extrinsically-induced apoptosis in a population of cells, comprising treating the cell population with a synergistically combined composition comprising an amount of TRAIL in conjunction with an amount of at least one reagent acting on mitochondrial pathways of the cells, which in combination is sufficient to induce cellular apoptosis, such that the apoptosis-inducing effect of the combination is greater than that of TRAIL alone, or the at least one reagent alone, or the additive individual apoptotic effects of TRAIL and the at least one reagent. However, TRAIL-sensitive normal cells are protected from the extrinsically induced apoptosis by treatment with a specific caspase inhibitor, such as a caspase 9 inhibitor. Consequently, in accordance with the present invention, TRAIL-resistant cancer cells are treated and killed with an apoptosis-inducing amount of the TRAIL combination, but the normal cells are protected or rescued from apoptosis by treatment with the specific caspase inhibitor.