ArticleThe pharmacogenomics journal2005
Correlating gene expression with chemical scaffolds of cytotoxic agents: ellipticines as substrates and inhibitors of MDR1.
Article in The pharmacogenomics journal, 2005. 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, 38 citations in OpenAlex.
- Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms.Oncotarget · 2016Article
- An integrative analysis of small molecule transcriptional responses in the human malaria parasite Plasmodium falciparum.BMC genomics · 2015Article
- Impact of terminal dimethylation on the resistance profile of α-N-heterocyclic thiosemicarbazones.Biochemical pharmacology · 2012Article
- Identification of compounds selectively killing multidrug-resistant cancer cells.Cancer research · 2009Article
- Pharmacogenomics approach reveals MRP1 (ABCC1)-mediated resistance to geldanamycins.Pharmaceutical research · 2009Article
- Chemogenomic analysis identifies geldanamycins as substrates and inhibitors of ABCB1.Pharmaceutical research · 2007Article
- Prediction of anticancer drug potency from expression of genes involved in growth factor signaling.Pharmaceutical research · 2006Article
- Linking pathway gene expressions to the growth inhibition response from the National Cancer Institute's anticancer screen and drug mechanism of action.The pharmacogenomics journal · 2005Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
To facilitate a systematic study of chemoresistance across diverse classes of anticancer drug candidates, we performed correlation analyses between cytotoxic drug potency and gene expression in 60 tumor cell lines (NCI-60; NCI-National Cancer Institute). Ellipticine analogs displayed a range of correlation coefficients (r) with MDR1 (ABCB1, encoding multidrug resistance (MDR) protein MDR1 or P-glycoprotein). To determine MDR1 interactions of five ellipticines with diverse MDR1-r values, we employed MDR1-transport and cytotoxicity assays, using MDR1 inhibitors and siRNA-mediated MDR1 downregulation, in MDR1-overexpressing cells. Ellipticines with negative correlations-indicative of MDR1-mediated resistance-were shown to be MDR1 substrates, whereas those with neutral or positive correlations served as MDR1 inhibitors, which escape MDR1-mediated chemoresistance. Correlation with additional genes in the NCI-60 confirmed topoisomerases as ellipticine targets, but suggested distinct mechanisms of action and chemoresistance among them, providing a guide for selecting optimal drug candidates.
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