Verapamil enhances the sensitivity of oxaliplatin to tumor cells by influencing the PARP pathway

Pharmazie. 2019 Dec 1;74(12):740-743. doi: 10.1691/ph.2019.9715.

Abstract

PARP is a DNA damage-modifying enzyme present in most eukaryotic cells. In this study, reverse docking showed that verapamil (Vera), which can effectively bind PARP1/2, could significantly inhibit PARP1/2 activity inside and outside the system. Moreover, it could enhance the sensitivity of oxaliplatin to low-expression P-glycoprotein (P-gP) tumor cells and strengthen its apoptosis-inducing effect on tumor cells under the reverse drug resistance concentration of tumor cells. Vera, which can reverse chemotherapy resistance of tumor cells, showed no simple correlations with oxaliplatin drug resistance or P-gP expression and could enhance the anti-tumor effect of platinum chemotherapeutic agents by influencing the PARP pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Oxaliplatin / pharmacology*
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*
  • Verapamil / pharmacology*

Substances

  • Antineoplastic Agents
  • Oxaliplatin
  • Verapamil
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1