Abstract
Chemotherapy and radiation therapy for cancer often have severe side effects that limit their efficacy. Because these effects are in part determined by p53-mediated apoptosis, temporary suppression of p53 has been suggested as a therapeutic strategy to prevent damage of normal tissues during treatment of p53-deficient tumors. To test this possibility, a small molecule was isolated for its ability to reversibly block p53-dependent transcriptional activation and apoptosis. This compound, pifithrin-alpha, protected mice from the lethal genotoxic stress associated with anticancer treatment without promoting the formation of tumors. Thus, inhibitors of p53 may be useful drugs for reducing the side effects of cancer therapy and other types of stress associated with p53 induction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / adverse effects*
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects*
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Benzothiazoles
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Cell Division / drug effects
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Cell Line
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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DNA / biosynthesis
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DNA Damage
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G2 Phase / drug effects
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Gamma Rays / adverse effects*
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Nude
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Neoplasms / drug therapy
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Neoplasms / radiotherapy
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Neoplasms / therapy*
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Radiation Tolerance / drug effects*
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Thiazoles / pharmacology*
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Time Factors
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Toluene / analogs & derivatives*
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Toluene / pharmacology
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / antagonists & inhibitors*
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Tumor Suppressor Protein p53 / physiology
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Ultraviolet Rays / adverse effects
Substances
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Antineoplastic Agents
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Benzothiazoles
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Thiazoles
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Tumor Suppressor Protein p53
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Toluene
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DNA
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pifithrin