Heat Shock Protein 70 Inhibits Apoptosis in Cancer Cells Through Simultaneous and Independent Mechanisms

Academic Article

Abstract

  • Background & Aims: Heat shock proteins (HSPs) are highly conserved and serve a multitude of functions that mediate cell survival. HSP70, the only inducible form of the 70-kilodalton subfamily of HSPs, is overexpressed in pancreatic cancer cells and has been shown to inhibit caspase-dependent apoptosis. We aimed to elucidate the mechanism by which HSP70 inhibits apoptosis in cancer cells. Methods: HSP70 expression was down-regulated in cultured pancreatic cancer cells by exposure to quercetin, triptolide, or short interfering RNAs. Intracellular Ca2+, cytosolic cathepsin B activity, caspase-3 activity, cell viability, and lysosome integrity were measured using colorimetric assays. Immunofluorescence assays were used to localize cathepsin B and Lamp2. BAPTA-AM was used to chelate intracellular Ca2+. Results: Inhibition of HSP70 increased intracellular Ca2+ levels in pancreatic and colon cancer cell lines and led to loss of lysosome integrity in pancreatic cancer cells. The release of intracellular Ca2+ and lysosomal enzymes activated caspase-dependent apoptosis independently and simultaneously. Conclusions: HSP70 inhibits apoptosis in cancer cells by 2 mechanisms: attenuation of cytosolic calcium and stabilization of lysosomes. HSP70-mediated cell survival might occur in other types of cancer cells. © 2009 AGA Institute.
  • Published In

  • Gastroenterology  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23751105
  • Author List

  • Dudeja V; Mujumdar N; Phillips P; Chugh R; Borja-Cacho D; Dawra RK; Vickers SM; Saluja AK
  • Start Page

  • 1772
  • End Page

  • 1782
  • Volume

  • 136
  • Issue

  • 5