The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo

S Radel; I Bankusli; E Mayhew; Y M Rustum

doi:10.1007/BF00262733

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The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo

Journal article

Peer reviewed

The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo

S Radel, I Bankusli, E Mayhew and Y M Rustum

Cancer chemotherapy and pharmacology, Vol.21(1), pp.25-30

1988

DOI: 10.1007/BF00262733

PMID: 3342462

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Abstract

DMDP [N-(3,4-dimethoxyphenethyl)-N-methyl-2-(2-naphthyl-m-dithane- 2-propylamine] a recently developed calcium antagonist analogue, caused a greatly increased intracellular retention of adriamycin and concomitant enhanced cytotoxicity in adriamycin-resistant P388 leukemia cells in vitro. These effects of DMDP were greater than those of another calcium channel blocker, verapamil, and occurred at one-half the dosage levels. Only slight enhancement in adriamycin toxicity was observed for either of these agents in the adriamycin-sensitive parental cell line. However, no significant therapeutic potentiation of adriamycin activity occurred with either verapamil or DMDP treatment in vivo. In vivo maximum DMDP tumor intracellular concentrations, as analyzed by HPLC, were the same in vitro tumor cell levels required to overcome adriamycin resistance. This inability to overcome drug resistance in vivo at acceptable levels of host toxicity is not only a function of maintaining necessary calcium antagonist concentrations in resistant tumor cells.

Animals

Calcium Channel Blockers - pharmacology

Doxorubicin - metabolism

Doxorubicin - pharmacology

Drug Resistance

Drug Synergism

Female

Glycoproteins - metabolism

Leukemia P388 - drug therapy

Leukemia P388 - metabolism

Leukemia, Experimental - drug therapy

Mice

Mice, Inbred DBA

Propylamines - pharmacology

Tumor Cells, Cultured - drug effects

Verapamil - pharmacology

Details

Title: Subtitle: The effects of verapamil and a tiapamil analogue, DMDP, on adriamycin-induced cytotoxicity in P388 adriamycin-resistant and -sensitive leukemia in vitro and in vivo
Creators: S Radel - Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, NY 14263
I Bankusli - Roswell Park Cancer Institute
E Mayhew - Roswell Park Cancer Institute
Y M Rustum - Roswell Park Cancer Institute
Resource Type: Journal article
Publication Details: Cancer chemotherapy and pharmacology, Vol.21(1), pp.25-30
DOI: 10.1007/BF00262733
PMID: 3342462
ISSN: 0344-5704
eISSN: 1432-0843
Grant note: CA 18420 / NCI NIH HHS CA 28494 / NCI NIH HHS
Language: English
Date published: 1988
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359955902771

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