PMID: 11901227Mar 20, 2002Paper

Down-regulation of DNA topoisomerase IIalpha in human colorectal carcinoma cells resistant to a protoberberine alkaloid, berberrubine

Molecular Pharmacology
Mi Ran Kang, In Kwon Chung

Abstract

Berberrubine, a protoberberine alkaloid that exhibits antitumor activity in animal models, has been identified as a specific poison of DNA topoisomerase II in vitro. To better understand the mechanisms of cellular response to berberrubine, human colorectal carcinoma cells (AMC5) were selected for resistance to berberrubine. The resulting cell line (AMC5/B1) was 5.3-fold resistant to berberrubine in the absence of MDR1 overexpression. The AMC5/B1 line was cross-resistant to topoisomerase II-targeted drugs but showed no cross-resistance to other antitumor drugs. The patterns of cross-resistance to various drugs led us to examine the cellular contents of topoisomerase II. Topoisomerase II activity was approximately 2.8-fold lower in AMC5/B1 cells compared with parental cells. The AMC5/B1 line contained approximately 5-fold decrease in topoisomerase IIalpha protein level and approximately 2.5-fold decrease in topoisomerase IIalpha mRNA level. A comparison of the degradation kinetics of topoisomerase IIalpha mRNA demonstrated that there was no difference in mRNA stability between the two cell lines. Furthermore, the activity of topoisomerase IIalpha promoter in AMC5/B1 cells was about 25% of that in AMC5 parental cells when transien...Continue Reading

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Citations

Dec 9, 2003·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jérôme KluzaChristian Bailly
Aug 26, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luis Miguel Guamán OrtizAnna Ivana Scovassi
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