Publication Date:
1999-09-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Komarov, P G -- Komarova, E A -- Kondratov, R V -- Christov-Tselkov, K -- Coon, J S -- Chernov, M V -- Gudkov, A V -- CA60730/CA/NCI NIH HHS/ -- CA75179/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1733-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10481009" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antineoplastic Agents/*adverse effects/pharmacology
;
Apoptosis/*drug effects
;
Benzothiazoles
;
Cell Division/drug effects
;
Cell Line
;
Cell Nucleus/drug effects/metabolism
;
Cytoplasm/drug effects/metabolism
;
DNA/biosynthesis
;
DNA Damage
;
G2 Phase/drug effects
;
Gamma Rays/*adverse effects
;
Humans
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mice, Nude
;
Neoplasms/drug therapy/radiotherapy/*therapy
;
Radiation Tolerance/*drug effects
;
Thiazoles/*pharmacology
;
Time Factors
;
Toluene/*analogs & derivatives/pharmacology
;
Tumor Cells, Cultured
;
Tumor Suppressor Protein p53/*antagonists & inhibitors/physiology
;
Ultraviolet Rays/adverse effects
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
