Effect of antiestrogens on leukemic cells: Relevance to drug resistance

A. Dvilanskv, L. Atlas, I. Nathan

Research output: Contribution to journalArticlepeer-review

Abstract

Two non-steroidal triphenylethylene antiestrogens, tamoxifen and chlomiphene were used. The latter has a longer dialkyl amino group than tamoxifen and has a higher affinity to antiestrogen binding sites. A third non-steroidal non-triphenylethylene antiestrogen, nafoxidine, which possesses a pyrrolidino group was used as well. The cytotoxic effects of the drugs on CEM/CCRF lymphoblastic leukemia cell line and its variants cell lines ,which are resistant to actinomycin D or vincristine were studied. Dose dependent cytotoxic activity of the drugs per se showed higher sensitivity of the parental cell line as compared to the resistant variants. Nafoxidine exerted the strongest cytotoxic effect and was the most efffective drug in reversal of drug resistance. The interrelationship of calcium channel blockers and antiestrogens cytotoxicity revealed advantage of the combined treatment. Evidence for phosphorylation/dephosphorylation processes related to these biological effects was found. These results suggest clinical potential use of antiestrogens in combination with other modifiers of drug resistance.

Original languageEnglish
Pages (from-to)872
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
StatePublished - 1 Dec 1997

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