Involvement of oncogenic protein β-catenin in LPS-induced cytotoxicity in mouse mononuclear leukemia RAW 264.7 cells

Naoki Koide, Yoshikazu Naiki, Erdenezaya Odkhuu, Bilegtsaikhan Tsolmongyn, Takayuki Komatsu, Kiyoaki Ito, Tomoaki Yoshida, Takashi Yokochi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A toll-like receptor 4 (TLR-4) ligand, lipopolysaccharide (LPS) not only activates expression and secretion of inflammatory cytokines, but it also often shows toxicity in monocytes. Whether an oncogenic protein, β-catenin, is positively involved in LPS-induced cytotoxicity in a mouse leukemic monocyte cell line, RAW 264.7, was examined. TWS119, a GSK-3β inhibitor, increased LPS-induced β-catenin accumulation in the nucleus and augmented LPS-induced cytotoxicity. Cardamonin, a β-catenin inhibitor, inhibited LPS-induced β-catenin accumulation in the nucleus and reduced LPS-induced cytotoxicity. To confirm that β-catenin is involved in LPS-induced cytotoxicity, silencing of β-catenin expression by siRNA was carried out. The results were that knockdown of β-catenin reduced LPS-induced cytotoxicity. Interestingly, Cardamonin treatment or β-catenin silencing reduced LPS-induced endoplasmic reticulum (ER) stress responses such as PERK and e1F-2α phosphorylation and CHOP expression. Moreover, TWS119 increased LPS-induced ER stress responses. On the basis of these results, the oncogenic protein β-catenin is considered to be positively involved in LPS-induced cytotoxicity, possibly by downregulating ER stress responses.

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalOncology Research
Volume21
Issue number1
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Koide, N., Naiki, Y., Odkhuu, E., Tsolmongyn, B., Komatsu, T., Ito, K., Yoshida, T., & Yokochi, T. (2013). Involvement of oncogenic protein β-catenin in LPS-induced cytotoxicity in mouse mononuclear leukemia RAW 264.7 cells. Oncology Research, 21(1), 59-65. https://doi.org/10.3727/096504013X13793555706803