TRAIL-induced activation of Akt catalytic activity and phosphorylation were highly correlated with p38/HSP27 phosphorylation, whereas the phosphorylation of p38/HSP27 increased further during incubation with curcumin and TRAIL, which caused significant apoptotic cell death in DU-145 cells. Next, we investigated whether the cellular level of HSP27 phosphorylation acts as a determinant of cell fate: from cell survival to cell death by biphasic way using another anticancer agent, gemcitabine an antitumor drug currently used for the treatment of advanced pancreatic cancer. We have observed that gemcitabine induced p38/HSP27 phosphorylation and acquired resistance at lower concentration as TRAIL did. After the acquisition of TRAIL or gemcitabine resistance, cancer cells (DU-145 or Mia-PaCa) with acquired resistance to these drugs expressed higher amount of vimentin as well as various MMPs. However, the expression level of these proteins even in TRAIL or gemcitabine-resistant cells was significantly decreased by the incorporation of constitutively phospho-mimic HSP27 with concurrent cell death, providing a new potential strategy to overcome the drug resistance and ultimate metastasis.

Citation Format: Dongxu Kang, Hye J. Choi, Jina Kim, Joo-Hang Kim, Jae Jin Song. Cellular level of HSP27 phosphorylation plays a key switch from cell survival to death induced by TRAIL or gemcitabine. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2957. doi:10.1158/1538-7445.AM2013-2957