| The p53-reactivating small-molecule RITA enhances cisplatin-induced cytotoxicity and apoptosis in head and neck cancer. | |
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MedLine Citation:
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PMID: 22634494 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We evaluated whether the restoration of p53 function by the p53-reactivating small molecule RITA (reactivation of p53 and induction of tumor cell apoptosis enhances cisplatin-induced cytotoxicity and apoptosis in head-and-neck cancer (HNC). RITA induced prominent accumulation and reactivation of p53 in a wild-type TP53-bearing HNC cell line. RITA showed maximal growth suppression in tumor cells showing MDM2-dependent p53 degradation. RITA promoted apoptosis in association with upregulation of p21, BAX, and cleaved caspase-3; notably, the apoptotic response was blocked by pifithrin-α, demonstrating its p53 dependence. With increasing concentrations, RITA strongly induced apoptosis rather than G2-phase arrest. In combination therapy, RITA enhanced cisplatin-induced growth inhibition and apoptosis of HNC cells invitro and in vivo. Our data suggest that the restoration of p53 tumor-suppressive function by RITA enhances the cytotoxicity and apoptosis of cisplatin, an action that may offer an attractive strategy for treating HNC. |
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Authors:
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Jong-Lyel Roh; Jung Ho Ko; Soo Jin Moon; Chang Hwan Ryu; Jun Young Choi; Wayne M Koch |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-5-22 |
Journal Detail:
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Title: Cancer letters Volume: - ISSN: 1872-7980 ISO Abbreviation: - Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-5-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Ireland Ltd. |
Affiliation:
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Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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