Regulation of tumor cell apoptotic sensitivity during the cell cycle (Review).
Understanding how current chemotherapeutic modalities induce apoptosis is critical to designing better anti-cancer agents. This review is concerned with how pharmacological agents induce tumor cell apoptosis in a cell cycle-dependent manner. Recent experiments demonstrate that expression of several apoptotic regulatory proteins (such as Bcl-2, Bax, p53, and Survivin) are differentially regulated according to the phases of the cell cycle. This cell cycle-dependent regulation in turn contributes to increased drug sensitivity in different phases of the cell cycle. It is therefore likely that the cell cycle-dependent expression of cell death proteins plays a role in regulating chemosensitivity and apoptotic commitment of human tumor cells.
Smith
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DM
Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Department of Biochemistry & Molecular Biology, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Gao
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Zhang
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Wang
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G
Dou
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QP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein