Heat-shock pretreatment inhibits sorbitol-induced apoptosis in K562, U937 and HeLa cells

Gabriella Marfe, Bruna Pucci, Luisa De Martino, Filomena Fiorito, Carla Di Stefano, Manuela Indelicato, Michele Aventaggiato, Matteo A. Russo, Marco Tafani

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to determine whether heat-shock pretreatment exerted a protective effect against sorbitol-induced apoptotic cell death in K562, U937 and HeLa cell lines and whether such protection was associated with a decreased cytochrome c release from mithocondria and a decreased activation of caspase-9 and -3. Following heat-shock pretreatment (42 ± 0.3°C for 1 hr), these cell lines were exposed to sorbitol for 1 hr. Apoptosis was evaluated by DNA fragmentation, whereas caspase-9,-3 activation, cytochrome c release and heat-shock protein70 (HSP70) were assayed by Western Blot. Sorbitol exposure-induced apoptosis in these different cell lines with a marked activation of caspase-9 and caspase-3, whereas heat-shock pretreatment before sorbitol exposure, induced expression of HSP70 and inhibited sorbitol-mediated cytochrome c release and subsequent activation of caspase-9 and caspase-3. Similarly, overexpression of HSP70 in the three cell lines studied prevented caspase-9 cleavage and activation as well as cell death. Furthermore, we showed that the mRNA expression of iNOS decreased during both the heat-shock treatment and heat-shock pretreatment before sorbitol exposure. By contrast, the expression of Cu-Zn superoxide dismutase (SOD) and Mn-SOD proteins increased during heat-shock pretreatment before sorbitol exposure. We conclude that, heat-shock pretreatment protects different cell lines against sorbitol-induced apoptosis through a mechanism that is likely to involve SOD family members.

Original languageEnglish
Pages (from-to)2077-2085
Number of pages9
JournalInternational Journal of Cancer
Volume125
Issue number9
DOIs
Publication statusPublished - Nov 1 2009

Keywords

  • Cu-Zn-SOD
  • Heat shock
  • HSP70
  • Mn-SOD
  • ROS
  • Sorbitol

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)
  • Oncology

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