Monensin inhibits proliferation, migration, and promotes apoptosis of breast cancer cells via downregulating UBA2

Drug Dev Res. 2020 Sep;81(6):745-753. doi: 10.1002/ddr.21683. Epub 2020 May 27.

Abstract

Breast cancer is a malignant tumor that occurs in the epithelial tissue of the breast gland, the morbidity, and mortality of which continue to increase. Therefore, it is crucial to find new drugs to treat breast cancer. Monensin is a carrier antibiotic that has been reported to inhibit the growth of cancer cells; however, its impacts on breast cancer cells have not been reported. In this article, the cell survival rate was measured by CCK-8. Colony formation assay was utilized to detect the level of cell proliferation. Transwell was used to measure the ability of cell invasion, and wound healing was used to measure the ability of cell migration. RT-qPCR and western blot were, respectively, used to detect the expression of related genes and proteins. The level of apoptosis was detected by flow cytometry. Cell transfection technique was used for overexpressing UBA2. We found that Monensin inhibited the proliferation and migration of breast cancer cells and inhibited the expression of MMP-2 and MMP-9. In addition, Monensin promoted the apoptosis accompanied by the increase of Bax, caspase3, caspase7, and caspase9 and the decreased of bcl-2 of breast cancer cells. Monensin was also found to inhibit UBA2 expression in breast cancer cells. Subsequently, after overexpression of UBA2, the impacts of Monensin on proliferation, migration, and apoptosis of breast cancer cells was inhibited. In conclusion, Monensin can inhibit the proliferation and migration and activate apoptosis of breast cancer cells via downregulating the expression of UBA2.

Keywords: Monensin; UBA2; apoptosis; breast cancer; migration; proliferation.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Female
  • Humans
  • Monensin / pharmacology*
  • Ubiquitin-Activating Enzymes / genetics
  • Ubiquitin-Activating Enzymes / metabolism*
  • Wound Healing / drug effects

Substances

  • Antineoplastic Agents
  • UBA2 protein, human
  • Monensin
  • Ubiquitin-Activating Enzymes