B-859-35, a new drug with anti-tumor activity reverses multi-drug resistance.
It has previously been shown that B-859-35 ((-)-3-methyl-5- 3-(4,4-diphenyl-l-piperidinyl)-propyl-l,4-dihydro- 2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate-hydrochloride) exerts a selective carcinostatic effect on some tumors. In order to evaluate whether the anti-cancer activity of B-859-35 can be modulated, we combined the new drug with several established anti-tumor drugs. A combination of B-859-35 with VP-16 (etoposide) in MDR(multi-drug-resistant-gene)-expressing Walker rat carcinoma cells shows synergism. A combination of B-859-35 with doxorubicin results in stronger synergism than verapamil/doxorubicin, especially at low concentrations of B-859-35. The resistance of mdrl(human multi-drug-resistance-gene)-expressing human HeLa KB-8-5 cells to doxorubicin can be reversed with non-toxic or weakly toxic concentrations of B-859-35 to the sensitivity of the parent KB-3-l cells. The finding that an anti-tumor drug is able to reverse multi-drug resistance makes B-859-35 an interesting drug for cancer treatment.
Hofmann
J
J
Institute of Medicinal Chemistry and Biochemistry, University of Innsbruck, Austria.
Ueberall
F
F
Egle
A
A
Grunicke
H
H
D000199:Actins / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002279:Carcinoma 256, Walker; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004095:Dihydropyridines / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D008325:Mammary Neoplasms, Experimental; D015394:Molecular Structure; D051381:Rats
D000199:Actins; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005047:Etoposide; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II; C054074:niguldipine