ArticleBritish journal of cancer1999
Reversal of MDR1-associated resistance to topotecan by PAK-200S, a new dihydropyridine analogue, in human cancer cell lines.
Article in British journal of cancer, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 26 citations in OpenAlex.
- Cardioprotective Effect against Ischemia-Reperfusion Injury of PAK-200, a Dihydropyridine Analog with an Inhibitory Effect on ClBiomolecules · 2023Article
- Effect ofInternational journal of molecular sciences · 2022Article
- Analysis of MDR genes expression and cross-resistance in eight drug resistant ovarian cancer cell lines.Journal of ovarian research · 2016Article
- Diethyl 4-(biphenyl-4-yl)-2,6-dimethyl-1,4-di-hydro-pyridine-3,5-di-carboxyl-ate.Acta crystallographica. Section E, Structure reports online · 2014Article
- MDR gene expression analysis of six drug-resistant ovarian cancer cell lines.BioMed research international · 2013Article
- BCRP transports dipyridamole and is inhibited by calcium channel blockers.Pharmaceutical research · 2005Article
- ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal.Cancer cell international · 2005Article
- Membrane transport of camptothecin: facilitation by human P-glycoprotein (ABCB1) and multidrug resistance protein 2 (ABCC2).BMC medicine · 2004Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent data suggest that expression of the membrane P170-glycoprotein (P-gp) may confer resistance to the topoisomerase-I-interactive agent topotecan. The present study describes the cellular effects of a new dihydropyridine analogue, PAK-200S, on P-gp-mediated resistance to topotecan in human breast and ovarian tumour cells. PAK-200S at a non-cytotoxic concentration of 2.0 microM completely reversed resistance to topotecan in P-gp-expressing MCF-7/adr (breast) and A2780/Dx5 (ovarian) tumour cells, respectively, with no effects on parental cells. Cellular pharmacokinetic studies by reversed-phase high-performance liquid chromatography analysis showed significantly lower cellular drug concentrations of the pharmacologically active closed-ring lactone of topotecan in multidrug-resistant cells than in parental cells. PAK-200S was effective in restoring the cellular lactone concentrations of topotecan in resistant MCF-7/adr cells to levels comparable to those obtained in parental cells. Furthermore, exposure of MCF-7/adr cells to topotecan in the presence of PAK-200S significantly increased the induction of protein-linked DNA breaks. PAK-200S did not alter nuclear topoisomerase I-mediated ex vivo pBR322 DNA plasmid unwinding activity and topoisomerase-I protein expression. These results suggest that reversal of P-gp-mediated resistance to topotecan by PAK-200S was related to the restoration of cellular drug concentrations of the active lactone form of topotecan rather than a direct effect on topoisomerase-I function.
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