New Trends for Antimalarial Drugs: Synergism between Antineoplastics and Antimalarials on Breast Cancer Cells

Biomolecules. 2020 Dec 1;10(12):1623. doi: 10.3390/biom10121623.

Abstract

Chemotherapy plays a key role in breast cancer therapy, but drug resistance and unwanted side effects make the treatment less effective. We propose a new combination model that combines antineoplastic drugs and antimalarials for breast cancer therapy. Cytotoxic effects of two antineoplastic agents alone and in combination with several antimalarials on MCF-7 tumor cell line was evaluated. Different concentrations in a fixed ratio were added to the cultured cells and incubated for 48 h. Cell viability was evaluated using MTT and SRB assays. Synergism was evaluated using the Chou-Talalay method. The results indicate doxorubicin (DOX) and paclitaxel (PTX) alone at concentrations of their IC50 and higher are cell growth inhibitors. Mefloquine, artesunate, and chloroquine at concentrations of their IC50 demonstrate anti-cancer activity. In combination, almost all antimalarials demonstrate higher ability than DOX and PTX alone to decrease cell viability at concentrations of IC50 and lower than their IC50. The combination of chloroquine, artesunate and mefloquine with DOX and PTX was synergic (CI < 1). The combination of DOX and mefloquine after 48 h incubation demonstrated the highest cytotoxicity against MCF-7 cells, and the combination of DOX and artesunate was the most synergic. These results suggest antimalarials could act synergistically with DOX/PTX for breast cancer therapy.

Keywords: antimalarial drugs; antineoplastic drugs; breast cancer; combination therapy; drug repurposing; drug synergism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / pharmacology*
  • Antimalarials / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Cell Survival / drug effects
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Synergism
  • Humans
  • MCF-7 Cells
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use

Substances

  • Antimalarials
  • Antineoplastic Agents
  • Doxorubicin
  • Paclitaxel