Back to Search
Start Over
Enhanced in vitro cytotoxicity of idarubicin compared to epirubicin and doxorubicin in rat prostate carcinoma cells.
- Source :
-
European urology [Eur Urol] 1997; Vol. 31 (3), pp. 365-70. - Publication Year :
- 1997
-
Abstract
- 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.<br />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.<br />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.<br />Conclusion: 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.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B, Member 1 biosynthesis
Animals
Antibiotics, Antineoplastic therapeutic use
Carcinoma pathology
Carcinoma secondary
Cell Division drug effects
Doxorubicin therapeutic use
Drug Resistance, Multiple
Epirubicin therapeutic use
Humans
Idarubicin therapeutic use
KB Cells cytology
KB Cells drug effects
Lethal Dose 50
Male
Prostatic Neoplasms pathology
Rats
Tumor Cells, Cultured
Antibiotics, Antineoplastic pharmacology
Carcinoma drug therapy
Doxorubicin pharmacology
Epirubicin pharmacology
Idarubicin pharmacology
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0302-2838
- Volume :
- 31
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European urology
- Publication Type :
- Academic Journal
- Accession number :
- 9129933
- Full Text :
- https://doi.org/10.1159/000474485