B-859-35, A NEW DRUG WITH ANTITUMOR-ACTIVITY REVERSES MULTIDRUG 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-hydrochlooride) 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 nontoxic or weakly toxic concentrations of B-859-35 to the sensitivity of the parent KB-3-1 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.