Cinnamylidene ketones as potential modulators of multidrug resistance in mouse lymphoma and human colon cancer cell lines.
The resistance to chemotherapy of cancer cells is mediated by the overexpression of P-glycoprotein, as an ATP-dependent membrane efflux pump. Two families of compounds have been screened, the cinnamylidenecycloalkanones and cinnamylidenebenzocycloalkanones, as promising multidrug resistance (MDR) reversal agents on mouse lymphoma and human colon cancer (COL0320) cell lines. The antiproliferative effects of the cinnamylidene derivatives were tested with the MTT method The MDR effect on drug accumulation was tested by flow cytometry. Combinations of resistance modifiers and cytostatics were tested on the two cell lines to obtain evidence for additive or synergistic interactions. Verapamil was applied as a resistance-modifying positive control. The best effects in the reversal of MDR in both cell lines were exhibited by the methoxy derivatives 2-(2-methaoxycinnamylidene)indan-1-one, 2-(2-methoxycinnamylidene)-3,4-dihydro-2H-naphthalen-1-one, 6-(2-methoxycinnamylidene)-6,7,8,9-tetrahydrocyclohepten-5-one), 2-cinnamylidene-3,4-dihydro-2H-naphthalen-1-one and 6-cinnamylidene-6,7,8,9-tetrahydrobenzocyclohepten-5-one. 2-(2-methoxycinnamylidene) indan-1-one and 2-(2-methoxy-cinnamylidene)-3,4-dihydro-2H-naphthalen-1-one were able to enhance the antiproliferative activity of doxorubicin in a synergistic way.
Engi
Helga
H
Department of Medical Microbiology and Immunobiology, Albert Szent-Györgyi Medical Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Gyémánt
Nóra
N
Lóránd
Tamás
T
Lévai
Albert
A
Ocsovszki
Imre
I
Molnár
Joseph
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D008223:Lymphoma / Q000473:pathology*; D051379:Mice
D007659:Ketones