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

Abstract

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/IKKα/IκBα/p65 NF-κB pathway. The activation of NF-κB pathway up-regulated downstream pro-apoptotic genes, TNF-α, TRAILR1 and TRAILR2, and triggered apoptosis through the extrinsic pathway, indicating that PP2A is a potential target for pancreatic cancer treatment.

• Authors: Wei Li, Zheng Chen, Yang Zong, Feiran Gong, Yi Zhu, Yunxia Zhu, Jinghuan Lv, Jingjing Zhang, Li Xie, Yujie Sun, Yi Miao, Min Tao, Xiao Han, Zekuan Xu
• Journal: Cancer letters (Cancer Lett) Vol. 304 Issue 2 Pg. 117-27 (May 28 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21376459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• NF-kappa B
• Okadaic Acid
• CHUK protein, human
• I-kappa B Kinase
• Protein Phosphatase 2
• Cantharidin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cantharidin (pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Enzyme Inhibitors (pharmacology)
• Humans
• I-kappa B Kinase (drug effects, metabolism)
• Mutagenesis, Site-Directed
• NF-kappa B (drug effects, metabolism)
• Okadaic Acid (pharmacology)
• Pancreatic Neoplasms (metabolism)
• Phosphorylation
• Protein Phosphatase 2 (antagonists & inhibitors)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Transfection