Apoptosis signal-regulating kinase 1-thioredoxin complex dissociation by capsaicin causes pancreatic tumor growth suppression by inducing apoptosis.

ABSTRACT:

Aim

In this study, we evaluated the effect of capsaicin on the interaction of redox-sensitive thioredoxin (Trx)/apoptosis signal-regulating kinase 1 (ASK1) in pancreatic cancer cells.

Results

Capsaicin treatment downregulated Trx and increased the phosphorylation (activation) of ASK1 at Thr845 and kinase activity in AsPC-1 and BxPC-3 cells. Capsaicin treatment also activated downstream effector molecules MKK4/7, caspase-9, and caspase-3. Antioxidants tiron or PEG-catalase blocked the activation of ASK1 cascade by capsaicin and protected the cells from apoptosis, indicating the involvement of reactive oxygen species in the activation of ASK1. Our results further revealed that Trx overexpression suppressed the effects of capsaicin, whereas ASK1 overexpression enhanced the apop

SUBMITTER: Pramanik KC 

PROVIDER: S-EPMC3437051 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature