Enhanced in vitro cytotoxicity of idarubicin compared to epirubicin and doxorubicin in rat prostate carcinoma cells.
OBJECTIVE
We evaluated the cytotoxic activity of the three anthracyclines, doxorubicin, epirubicin and idarubicin, in different sublines of the Dunning rat prostate carcinoma as well as in multidrug-resistant KB cells, expressing a high amount of the human multidrug resistance gene product, P glycoprotein.


METHODS
The effectiveness of the three anthracyclines was tested in vitro in the Dunning rat prostate carcinoma sublines G, AT.1, AT.3.1, MatLu, and MatLyLu, as well as in multidrug-resistant KB cells, using an MTT assay.


RESULTS
All drugs were clearly more effective in the androgen-sensitive Dunning rat prostate carcinoma subline G than in the androgen-independent growing sublines AT.1, AT.3.1, MatLu, and MatLyLu. Idarubicin was much more effective than doxorubicin or epirubicin. To further elucidate the mechanism of action of idarubicin as compared with doxorubicin and epirubicin, we tested the cytotoxicity of these anthracyclines in highly multidrug-resistant KB-V1 cells, which express high amounts of P glycoprotein, as well as in the drug-sensitive parental KB-3-1 cells. KB-V1 cells proved to be highly resistant to doxorubicin and epirubicin with IC50 values of 2,300 and 1,000 ng/ml, respectively. Idarubicin, however, was about 57.5-fold and 25-fold more active, respectively, suggesting, that it is able to overcome P-glycoprotein-mediated multidrug resistance.


CONCLUSIONS
The strong in vitro effectiveness of idarubicin in androgen-insensitive prostate carcinoma cells suggests that this drug might be useful in the treatment of hormone-refractory prostate carcinoma.
Siegsmund
M J
MJ
Department of Urology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
Stendler
A
A
Kreukler
C
C
Köhrmann
K U
KU
Alken
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D015251:Epirubicin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology* / Q000627:therapeutic use; D007624:KB Cells / Q000166:cytology / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D004317:Doxorubicin; D015255:Idarubicin