Počet záznamů: 1
Novel Inhibitors of Cyclin-Dependent Kinases Combat Hepatocellular Carcinoma without Inducing Chemoresistance
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SYSNO ASEP 0421049 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Novel Inhibitors of Cyclin-Dependent Kinases Combat Hepatocellular Carcinoma without Inducing Chemoresistance Tvůrce(i) Haider, C. (AT)
Grubinger, M. (AT)
Řezníčková, Eva (UEB-Q) RID, ORCID
Weiss, T.S. (DE)
Rotheneder, H. (AT)
Miklos, W. (AT)
Berger, W. (AT)
Jorda, Radek (UEB-Q) ORCID, RID
Zatloukal, M. (CZ)
Gucký, T. (CZ)
Strnad, Miroslav (UEB-Q) RID, ORCID
Kryštof, Vladimír (UEB-Q) RID, ORCID
Mikulits, W. (AT)Zdroj.dok. Molecular Cancer Therapeutics. - : American Association for Cancer Research - ISSN 1535-7163
Roč. 12, č. 10 (2013), s. 1947-1957Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova PRIMARY HUMAN HEPATOCYTES ; SELICICLIB R-ROSCOVITINE ; CELL-CYCLE Vědní obor RIV CE - Biochemie CEP GAP305/12/0783 GA ČR - Grantová agentura ČR GA301/08/1649 GA ČR - Grantová agentura ČR CEZ AV0Z50380511 - UEB-Q (2005-2011) UT WOS 000325548400003 DOI 10.1158/1535-7163.MCT-13-0263 Anotace Treatment options for hepatocellular carcinoma using chemotherapeutics at intermediate and advanced stages of disease are limited as patients most rapidly escape from therapy and succumb to disease progression. Mechanisms of the hepatic xenobiotic metabolism are mostly involved in providing chemoresistance to therapeutic compounds. Given the fact that the aberrant activation of cyclin-dependent kinases (CDK) is frequently observed in hepatocellular carcinomas, we focused on the efficacy of the novel compounds BA-12 and BP-14 that antagonize CDK1/2/5/7 and CDK9. Inhibition of those CDKs in human hepatocellular carcinoma cell lines reduced the clonogenicity by arresting cells in S-G(2) and G(2)-M phase of the cell cycle and inducing apoptosis. In contrast, primary human hepatocytes failed to show cytotoxicity and apoptosis. No loss of chemosensitivity was observed in hepatocellular carcinoma cells after long-term exposure to inhibitors. In vivo, treatment of xenografted human hepatocellular carcinomas with BA-12 or BP-14 effectively repressed tumor formation. Moreover, BA-12 or BP-14 significantly diminished diethylnitrosamine (DEN)-induced hepatoma development in mice. These data show that BA-12 or BP-14 exhibit strong antitumorigenic effects in the absence of chemoresistance, resulting in a superior efficacy compared with currently used chemotherapeutics in hepatocellular carcinomas. Pracoviště Ústav experimentální botaniky Kontakt David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Rok sběru 2014
Počet záznamů: 1