Anti-cancer drug characterisation using a human cell line panel representing defined types of drug resistance

Dhar, Sumeer; Nygren, Peter; Csòka, Katalin; Botling, Johan; Nilsson, Kenneth; Larsson, Rolf

doi:10.1038/bjc.1996.453

Cited by 61 publications

(61 citation statements)

References 33 publications

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“…In the present study, we studied the gene expression and drug activity in a panel of 10 cell lines representing different mechanisms of anticancer drug resistance. Previous studies have shown that drug activity patterns in this panel can be used to classify anticancer drugs according to mechanism of action (Dhar et al, 1996). Here we showed that this classification also corresponded to identifiable patterns of gene expression and that the genes which correlated to drug sensitivity and resistance seem to be biologically relevant.…”

Section: Discussionsupporting

confidence: 62%

“…The human cancer cell line panel has been described previously (Dhar et al, 1996). The panel consists of the parental cell lines RPMI 8226 (myeloma), CCRF-CEM (leukaemia), U937-GTB (lymphoma) and NCI-H69 (small-cell lung cancer); the drugresistant sublines 8226/Dox40 8226/LR5, CEM/VM-1, U937/vcr, H69AR and the primary resistant ACHN (renal adenocarcinoma).…”

Section: Cell Culturementioning

confidence: 99%

“…Rapid cell-based methods for high-throughput and focused screening based on drug-response analysis in a panel of cell lines have proven to be important tools in anticancer drug discovery and early evaluation (Paull et al, 1989;Boyd and Paull, 1995;Dhar et al, 1996;Weinstein et al, 1997). Research performed at the National Cancer Institute (NCI) has shown that a drug activity profile acquired from a nonclonogenic growth inhibition assay on a panel of 60 parental human cancer cell lines can provide important information on the mechanism of action of various compounds.…”

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confidence: 99%

“…Robust and accurate mechanistic drug -drug relationships have repeatedly been demonstrated using both simple correlation analysis and more sophisticated data analytical methods (Paull et al, 1989;Weinstein et al, 1992Weinstein et al, , 1997Boyd and Paull, 1995). We have previously shown that, by applying similar techniques, a smaller panel of 10 cell lines representing different drug-resistant phenotypes could accomplish accurate classifications of mechanisms of action for common anticancer drugs (Dhar et al, 1996).…”

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confidence: 99%

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Identification of molecular mechanisms for cellular drug resistance by combining drug activity and gene expression profiles

et al. 2005

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Acquired drug resistance is a major problem in cancer treatment. To explore the genes involved in chemosensitivity and resistance, 10 human tumour cell lines, including parental cells and resistant subtypes selected for resistance against doxorubicin, melphalan, teniposide and vincristine, were profiled for mRNA expression of 7400 genes using cDNA microarray technology. The drug activity of 66 cancer agents was evaluated on the cell lines, and correlations between drug activity and gene expression were calculated and ranked. Hierarchical clustering of drugs based on their drug -gene correlations yielded clusters of drugs with similar mechanism of action. Genes correlated with drug sensitivity and resistance were imported into the PathwayAssist software to identify putative molecular pathways involved. A substantial number of both proapoptotic and antiapoptotic genes such as signal transducer and activator of transcription 1, mitogen-activated protein kinase 1 and focal adhesion kinase were found to be associated to drug resistance, whereas genes linked to cell cycle control and proliferation, such as cell division cycle 25A and signal transducer of activator of transcription 5A, were associated to general drug sensitivity. The results indicate that combined information from drug activity and gene expression in a resistance-based cell line panel may provide new knowledge of the genes involved in anticancer drug resistance and become a useful tool in drug development.

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Section: Discussionsupporting

confidence: 62%

Section: Cell Culturementioning

confidence: 99%

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Identification of molecular mechanisms for cellular drug resistance by combining drug activity and gene expression profiles

et al. 2005

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“…by Dahr and co-workers. 3 Thus, sensitivity profiles of novel drugs with unknown mechanism of action can be compared to profiles of known drugs to formulate hypotheses on their mechanisms of action as well as be used to identify important structural characteristics by computing whether drugs with similar activity also have similar structural features.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Drug Sensitivity-Gene Expression Correlations Involve a Tissue of Origin Dependency

Andersson

Fryknäs

Rickardson

et al. 2006

J. Chem. Inf. Model.

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A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper shows that these discrepancies can be viewed as a weighting of drug−drug distances, the weights depending on which cell lines the two drugs differ in.

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Synthesis, Antimicrobial and Antineoplastic Activities for Agelasine and Agelasimine Analogs with a β‐Cyclocitral Derived Substituent

Proszenyák

Charnock

Hedner

et al. 2007

Archiv der Pharmazie

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Agelasines and agelasimines are antimicrobial and cytotoxic purine derivatives isolated from marine sponges (Agelas sp.). We have synthesized structurally simplified analogs of these natural products starting from beta-cyclocitral. The novel compounds were found to be strong inhibitors of a wide variety of pathogenic microorganisms (incl. Mycobacterium tuberculosis) as well as cancer cell lines. The biological activities were generally in the same range as those previously found for the structurally more complex agelasines and agelasimines isolated in small amounts from natural sources. We also report for the first time that agelasine and agelasimine analogs inhibit growth of protozoa (Acanthamoeba castellanii and Acanthamoeba polyphaga). Acanthamoeba keratitis is an increasingly common and severe corneal infection, closely associated with contact lens wear.

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Anti-cancer drug characterisation using a human cell line panel representing defined types of drug resistance

Abstract: Summary Differential drug response in a human cell line panel representing defined types of cytotoxic drug resistance was measured using the non-clonogenic fluorometric microculture cytotoxicity assay (FMCA)

Cited by 61 publications

References 33 publications

Identification of molecular mechanisms for cellular drug resistance by combining drug activity and gene expression profiles

Identification of molecular mechanisms for cellular drug resistance by combining drug activity and gene expression profiles

In Vitro Drug Sensitivity-Gene Expression Correlations Involve a Tissue of Origin Dependency

Synthesis, Antimicrobial and Antineoplastic Activities for Agelasine and Agelasimine Analogs with a β‐Cyclocitral Derived Substituent

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