Efficient induction of apoptosis by proteasome inhibitor: bortezomib in the human breast cancer cell line MDA-MB-231

Mol Cell Biochem. 2014 Apr;389(1-2):177-85. doi: 10.1007/s11010-013-1939-5. Epub 2014 Jan 3.

Abstract

The cellular and molecular effects of the proteasome inhibitor-bortezomib-on breast cancer cells are as yet poorly characterised. Bortezomib selectively induces apoptosis in some cancer cells. However, the nature of its selectivity remains unknown. Previously, we demonstrated that: there was no effect of bortezomib action on apoptosis and a time-dependent increase in senescence of human skin fibroblasts. The study presented here provides novel information on cellular effects of bortezomib in breast cancer cells line MDA-MB-231. Our findings demonstrated that in contrast to normal fibroblasts, bortezomib treatment evoked a strong effect on apoptosis in breast cancer cells incubated in hypoxic and normoxic conditions. We observed a time-dependent increase up to 70 % in apoptosis of MDA-MB-231 cells in hypoxic and normoxic conditions. There was no effect of bortezomib action on senescence of these cells. We suggest that bortezomib may be candidates for further evaluation as chemotherapeutic agents for human breast cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Boronic Acids / pharmacology*
  • Bortezomib
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Hypoxia / drug therapy
  • Hypoxia / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors / pharmacology*
  • Pyrazines / pharmacology*
  • beta-Galactosidase / metabolism

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • HSP70 Heat-Shock Proteins
  • Proteasome Inhibitors
  • Pyrazines
  • oxygen-regulated proteins
  • Bortezomib
  • beta-Galactosidase
  • Proteasome Endopeptidase Complex