The Interaction of Cisplatin with Signal Transduction Pathways and the Regulation of Apoptosis
There are many ways to kill a cell. In the absence of serum, cells usually die because they have lost a receptor-mediated survival signal. Some cells can be killed by engaging certain receptors such as during glucocorticoid-mediated killing of thymocytes. Cells can also be killed by a multitude of cytotoxic agents including cisplatin. These insults all have a common endpoint: the cells die by apoptosis. There is a network of signals, initially unique to each insult, but eventually converging on a common pathway, only the latter part of which can truly be considered apoptosis. For example, resistance to cisplatin may be mediated by altered drug accumulation, decreased DNA damage or increased DNA repair.1,2 These mechanisms may inhibit apoptosis induced by cisplatin, but they do not rescue a cell from most drugs, and they certainly do not rescue cells from removal of serum. In contrast, the Bcl-2 protein can protect cells from each of these insults, and therefore reflects a step much further along the pathway; a step that is common to multiple insults. Bcl-2 is the prototype of an anti-apoptotic protein, defined as a means to protect cells from multiple unrelated insults. With respect to cancer chemotherapy, Bcl-2 elicits a kind of non-specific multi-drug resistance.
KeywordsFocal Adhesion Kinase Okadaic Acid Intracellular Acidification Acute Myelogenous Leukemia Cell Human Acute Myelogenous Leukemia Cell
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