Phenylacetate: a novel nontoxic inducer of tumor cell differentiation.
Sodium phenylacetate was found to affect the growth and differentiation of tumor cells in vitro at concentrations that have been achieved in humans with no significant adverse effects. Treatment of promyelocytic leukemia HL-60 cells resulted in the rapid decline of myc oncogene expression followed by growth arrest and granulocyte differentiation. Phenylacetate also induced highly efficient adipocyte conversion in immortalized mesenchymal C3H 10T1/2 cultures; yet, unlike the differentiating chemotherapeutic drug 5-aza-2'-deoxycytidine, phenylacetate did not cause neoplastic transformation in these susceptible cells. The results indicate that phenylacetate is both effective in inducing tumor cell maturation and free of cytotoxic and carcinogenic effects, a combination that warrants attention to its potential use in cancer intervention.
Samid
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Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Shack
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Sherman
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D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D000077209:Decitabine; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D051379:Mice; D008819:Mice, Nude; D010648:Phenylacetates / Q000494:pharmacology*; D012335:RNA, Ribosomal / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D010648:Phenylacetates; D012335:RNA, Ribosomal; D000077209:Decitabine; C025136:phenylacetic acid; D001374:Azacitidine