Contributions of Apoptosis and Senescence to Cytotoxicity Produced by Microtubule-Stabilizing Agents

摘要: The antitumor drug Taxol is recognized for its efficacy in the treatment of cancer and has become prototype a class drugs known as microtubule-stabilizing agents (MSAs). Despite years investigation, clear detailed mechanism by which these compounds bring about tumor cell death remains elusive. Apoptosis, with well-defined biochemical cell-structural characteristics, often been presented most important direct result Taxol. It now that major response to MSAs far more complex depends on type, specific being studied, concentration exposed. Although apoptosis may occur at downstream step cells agents, it not demonstrated this effect binding target, microtubules, except hematopoietic cells. Other processes do follow directly from microtubules include caspase-independent death, or without an apoptotic morphology, characteristic aberrant mitosis referred mitotic catastrophe. These appear produce significant amount well after would be produced caspase activation. In addition killing, cytotoxic are elicit stress-induced, terminal proliferation premature accelerated senescence. This had thought play minor role actions MSAs, but recently, one such agent, discodermolide, was shown powerful induction senescence phenotype appeared seen invariably followed delayed form death. effects much promise perceived newer their widespread function many options they have inhibiting uncontrolled proliferation.