Recent advances in understanding the cell death pathways activated by anticancer therapy

Authors

  • Ryungsa Kim M.D., Ph.D.

    Corresponding author
    1. International Radiation Information Center, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
    • International Radiation Information Center, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8553, Japan
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Abstract

Over the past two decades, the role of apoptosis in the cytotoxicity of anticancer drugs has become clear. Apoptosis may occur via a death receptor-dependent (extrinsic) or independent (intrinsic or mitochondrial) pathway. Mitochondria play a central role in cell death in response to DNA damage, and mediate the interaction(s) of various cytoplasmic organelles, including the endoplasmic reticulum, Golgi apparatus, and lysosomes. The mitochondrial pathway of cell death is mediated by Bcl-2 family proteins, a group of antiapoptotic and proapoptotic proteins that regulate the passage of small molecules, such as cytochrome c, Smac/Diablo, and apoptosis-inducing factor, which activates caspase cascades, through the mitochondrial transition pore. In addition, apoptosis can induce autophagic cell death via crosstalk between the two pathways upon treatment with anticancer drugs. The current review focused on recent advances surrounding the mechanism(s) of cell death induced by anticancer agents and discussed potential molecular targets for enhancing the chemotherapeutic effect(s) of anticancer agents. Cancer 2005. © 2005 American Cancer Society.

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