B-859-35, a new drug with anti-tumor activity reverses multi-drug resistance

Int J Cancer. 1991 Apr 1;47(6):870-4. doi: 10.1002/ijc.2910470614.

Abstract

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.

MeSH terms

  • Actins / genetics
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Calcium Channel Blockers / pharmacology
  • Carcinoma 256, Walker
  • Cell Division / drug effects
  • Cell Line
  • DNA Topoisomerases, Type II / genetics
  • Dihydropyridines / pharmacology*
  • Doxorubicin / pharmacology
  • Drug Resistance / genetics
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Etoposide / pharmacology
  • HeLa Cells / cytology
  • HeLa Cells / drug effects
  • Humans
  • KB Cells
  • Mammary Neoplasms, Experimental
  • Molecular Structure
  • Rats

Substances

  • Actins
  • Antineoplastic Agents
  • Calcium Channel Blockers
  • Dihydropyridines
  • Etoposide
  • Doxorubicin
  • DNA Topoisomerases, Type II
  • niguldipine