Involvement of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2-aminophenoxazine-3-one in cancer cells

  • Authors:
    • Shota Moriya
    • Keisuke Miyazawa
    • Tomohiro Kawaguchi
    • Xiao-Fang Che
    • Akio Tomoda
  • View Affiliations

  • Published online on: Wednesday, June 8, 2011
  • Pages: 981-988
  • DOI: 10.3892/ijo.2011.1072

Abstract

In this study, 2-aminophenoxazine-3-one (Phx-3) exhibited a potent cell growth inhibitory effect with apoptotic features in a dose-dependent manner in various cancer cell lines tested. Comparison of the expression profiles of endoplasmic reticulum (ER) stress-related genes in U266 multiple myeloma cells after treatment with Phx-3 and the ER stress inducers tunicamycin (TNM) and thapsigargin (TPG) indicated that although TNM and TPG potently induced pro-apoptotic transcription factor CHOP (GADD153) within 8 h of treatment, Phx-3 induced almost no CHOP within 48 h of treatment in U266 cells. However, murine embryonic fibroblast (MEF) cells and other cancer cell lines (e.g. A549 lung cancer cells and HL-60 acute leukemia cells) exhibited up-regulation of CHOP after treatment with Phx-3. The potency of CHOP induction in response to Phx-3 appeared to be partially correlated with the cytotoxic sensitivity of Phx-3 among various cell lines tested. MEF cells derived from CHOP knockout mice were more resistant to Phx-3 than wild-type MEF cells. Since Phx-3 has been shown to induce activation of NF-κB, a transcription factor functioning as a repressor of CHOP, we further treated U266 cells with a combination of Phx-3 and NF-κB inhibitors (e.g. BAY11-7082 or parthenolide). This enhanced cytotoxicity along with up-modulation of CHOP in U266 cells. These data suggest that ER stress-mediated CHOP induction by Phx-3 is involved in the cytotoxic effect. Regulation of CHOP expression appears to be a potent therapeutic target for cancer treatment.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Moriya, S., Miyazawa, K., Kawaguchi, T., Che, X., & Tomoda, A. (2011). Involvement of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2-aminophenoxazine-3-one in cancer cells. International Journal of Oncology, 39(4), 981-988.
MLA
Moriya, Miyazawa, Kawaguchi, Che, and Akio Tomoda. "Involvement of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2-aminophenoxazine-3-one in cancer cells." International Journal of Oncology International Journal of Oncology 39.4 (2011): 981-988.
Chicago
Moriya, Miyazawa, Kawaguchi, Che, and Akio Tomoda. "Involvement of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2-aminophenoxazine-3-one in cancer cells." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 981-988.