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.
authors.affiliation: Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ushijima
authors.affiliation: Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Horyozaki
authors.affiliation: Department of Molecular Biology, School of Pharmacy, Iwate Medical University, 2-1-1, Nishitokuta, Yahaba, Shiwagun, Iwate 028-3694, Japan. Electronic address: mmaeda@nupals.ac.jp.
authors.forename: Masatomo
authors.initials: M
authors.lastname: Maeda
mesh_terms: D000841:Anisomycin / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage*; D050993:GATA6 Transcription Factor / Q000378:metabolism*; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000008:administration & dosage
chemical_list: D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; D005472:Fluorouracil
keywords: Anisomycin; Apoptosis; Cell cycle; GATA-6; Spheroid culture