Potential Anticancer Effect of Calcium-mediated Src Degradation on Hormone-dependent Breast Cancer

Anticancer Res. 2020 Apr;40(4):1989-1996. doi: 10.21873/anticanres.14154.

Abstract

Background/aim: The antitumor effect of sustained calcium supply on Src degradation was investigated in the context of hormone-dependent breast cancer, followed by elucidation of the underlying mechanisms.

Materials and methods: Hormone-dependent T-47D breast cancer cells were used. Lactate calcium salt (LCS) was used as the source of sustained calcium supply, and the applicable concentration of LCS was determined by the colorimetric MTT assay. LCS-mediated deactivation of downstream signaling via Src degradation was identified by western blot and immunocytochemistry.

Results: Calcium-mediated degradation of Src decreased survival signaling via phosphoinositide 3-kinase and protein kinase B and resulted in significant inhibition of the clonogenic ability of hormone-dependent breast cancer cells. Tumor volume was significantly decreased in response to LCS injection in a heterotopic xenograft model, and immuno histochemistry revealed tumor necrosis.

Conclusion: Sustained supply of calcium inhibited survival signaling via degradation of Src in hormone-dependent breast cancer cells.

Keywords: Breast cancer; Src; anticancer effect; calcium; hormone.

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Calcium / pharmacology
  • Cell Line, Tumor
  • Female
  • Humans
  • Lactic Acid / pharmacology
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / pathology
  • Oncogene Protein v-akt / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Proteolysis / drug effects*
  • Signal Transduction / drug effects
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / genetics*

Substances

  • Lactic Acid
  • src-Family Kinases
  • Oncogene Protein v-akt
  • Calcium