Ascofuranone has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we study the effects of ascofuranone on cell cycle progression in human cancer cells and find that ascofuranone induces G(1) arrest without cytoxicity with upregulation of p53 and p21(WAF1/CIP1) while downregulating c-Myc and G(1) cyclins. Chromatin immunoprecipitation assay and RNA interference studies with cells deficient in p53 and p21 show that ascofuranone induces p21(WAF1/CIP1) expression and subsequent G(1) arrest through the release of p21(WAF1/CIP1) promoter from c-Myc-mediated transcriptional repression, independent of p53. Ascofuranone-induced p21(WAF1/CIP1) associates with CDK2 and prevents CDK2-cyclin E complex formation, leading to the inactivation of E2F transcriptional activity.

Ascofuranone: a possible therapeutic tool for autosomal dominant polycystic kidney disease? / Cardinale, Vincenzo; Alvaro, Domenico. - In: MOLECULAR CANCER THERAPEUTICS. - ISSN 1535-7163. - 9:11(2010), pp. 3100-3100. [10.1158/1535-7163.mct-10-0741]

Ascofuranone: a possible therapeutic tool for autosomal dominant polycystic kidney disease?

CARDINALE, VINCENZO;ALVARO, Domenico
2010

Abstract

Ascofuranone has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we study the effects of ascofuranone on cell cycle progression in human cancer cells and find that ascofuranone induces G(1) arrest without cytoxicity with upregulation of p53 and p21(WAF1/CIP1) while downregulating c-Myc and G(1) cyclins. Chromatin immunoprecipitation assay and RNA interference studies with cells deficient in p53 and p21 show that ascofuranone induces p21(WAF1/CIP1) expression and subsequent G(1) arrest through the release of p21(WAF1/CIP1) promoter from c-Myc-mediated transcriptional repression, independent of p53. Ascofuranone-induced p21(WAF1/CIP1) associates with CDK2 and prevents CDK2-cyclin E complex formation, leading to the inactivation of E2F transcriptional activity.
2010
01 Pubblicazione su rivista::01a Articolo in rivista
Ascofuranone: a possible therapeutic tool for autosomal dominant polycystic kidney disease? / Cardinale, Vincenzo; Alvaro, Domenico. - In: MOLECULAR CANCER THERAPEUTICS. - ISSN 1535-7163. - 9:11(2010), pp. 3100-3100. [10.1158/1535-7163.mct-10-0741]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/115309
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