PP2A inhibitors induce apoptosis in pancreatic cancer cell line PANC-1 through persistent phosphorylation of IKKα and sustained activation of the NF-κB pathway

Serine/threonine protein phosphatase 2A (PP2A), is thought to be a cancer suppresser, as inhibition of PP2A can induce phosphorylation and activation of substrate kinases, most of which can accelerate growth. Interestingly, cantharidin potently inhibits PP2A but efficiently represses various cancer cells. In the present study, we found that PP2A inhibitors, cantharidin or Okadaic acid, inhibited cell viability and triggered apoptosis in PANC-1 pancreatic cancer cell line dependent on PP2A/IKK alpha/I kappa B alpha/p65 NF-kappa B pathway. The activation of NF-kappa B pathway up-regulated downstream pro-apoptotic genes, TNF-alpha, TRAILR1 and TRAILR2, and triggered apoptosis through the extrinsic pathway, indicating that PP2A is a potential target for pancreatic cancer treatment. (C) 2011 Elsevier Ireland Ltd. All rights reserved.