skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell

Abstract

Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. - Highlights: • Anisomycin induces proteolysis of GATA-6 in DLD-1 cells. • Anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest. • Anisomycin suppresses themore » growth of spheroids of DLD-1, and enhances the effect of 5-FU.« less

Authors:
; ;
Publication Date:
OSTI Identifier:
22606222
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 478; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTINOMYCIN; AMP; ANIMAL TISSUES; CARCINOMAS; CATTLE; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CHEMOTHERAPY; CONCENTRATION RATIO; DMSO; IMMUNOGLOBULINS; INDUCTION; INHIBITION; PEROXIDASES; PH VALUE; POTASSIUM CHLORIDES; PROTEOLYSIS; SODIUM; SODIUM CHLORIDES; SODIUM PHOSPHATES; SPHEROIDS; SULFATES; TRANSCRIPTION FACTORS; ULTRAVIOLET RADIATION; URACILS

Citation Formats

Ushijima, Hironori, Horyozaki, Akiko, and Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.05.139.
Ushijima, Hironori, Horyozaki, Akiko, & Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp. Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell. United States. doi:10.1016/J.BBRC.2016.05.139.
Ushijima, Hironori, Horyozaki, Akiko, and Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp. Fri . "Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell". United States. doi:10.1016/J.BBRC.2016.05.139.
@article{osti_22606222,
title = {Anisomycin-induced GATA-6 degradation accompanying a decrease of proliferation of colorectal cancer cell},
author = {Ushijima, Hironori and Horyozaki, Akiko and Maeda, Masatomo, E-mail: mmaeda@nupals.ac.jp},
abstractNote = {Transcription factor GATA-6 plays a key role in normal cell differentiation of the mesoderm and endoderm. On the other hand, GATA-6 is abnormally overexpressed in many clinical gastrointestinal cancer tissue samples, and accelerates cell proliferation or an anti-apoptotic response in cancerous tissues. We previously showed that activation of the JNK signaling cascade causes proteolysis of GATA-6. In this study, we demonstrated that anisomycin, a JNK activator, stimulates nuclear export of GATA-6 in a colorectal cancer cell line, DLD-1. Concomitantly, anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest in a plate culture. However, it did not induce apoptosis under growth arrest conditions. Furthermore, the growth of DLD-1 cells in a spheroid culture was suppressed by anisomycin. Although 5-FU showed only a slight inhibitory effect on 3D spheroid cultures, the same concentration of 5-FU together with a low concentration of anisomycin exhibited strong growth inhibition. These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. - Highlights: • Anisomycin induces proteolysis of GATA-6 in DLD-1 cells. • Anisomycin remarkably inhibits the proliferation of DLD-1 cells via G2/M arrest. • Anisomycin suppresses the growth of spheroids of DLD-1, and enhances the effect of 5-FU.},
doi = {10.1016/J.BBRC.2016.05.139},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 478,
place = {United States},
year = {Fri Sep 09 00:00:00 EDT 2016},
month = {Fri Sep 09 00:00:00 EDT 2016}
}