Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines

Journal of Pharmacological Sciences

Toshiyuki Sasaguri²  Fumi Takahashi-Yanaga²  Etsuko Matsuzaki³  Sachio Morimoto²  Yutaka Watanabe¹  Kentaro Jingushi²  Toshihisa Nakamura²  Tatsuya Yoshihara² 

[1] Department of Applied Chemistry, Faculty of Engineering, Ehime University, Japan;Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Japan;Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Japan

关键词: c-Myc;    Wnt/β-catenin signaling pathway;    colon cancer cell;    differentiation-inducing factor-1;    glycogen synthase kinase-3β;   

DOI  :  10.1254/jphs.12204FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(31)Cited-By(4)Differentiation-inducing factor-1 (DIF-1), a morphogen for Dictyostelium discoideum, inhibits the proliferation of human cancer cell lines by suppressing the Wnt/β-catenin signaling pathway. In this study, we examined the effect of DIF-1 on c-Myc, a target gene product of the Wnt/β-catenin signaling pathway, mainly using HCT-116 colon cancer cells. DIF-1 strongly reduced the amount of c-Myc protein in time- and concentration-dependent manners and reduced c-Myc mRNA expression by inhibiting promoter activity through the TCF binding sites. The effect of DIF-1 on c-Myc was also confirmed using the human cervical cell line HeLa. Pretreatment with the proteasome inhibitor MG132 or glycogen synthase kinase-3β (GSK-3β) inhibitors (LiCl and SB216763) attenuated the effect of DIF-1, suggesting that DIF-1 induced c-Myc protein degradation through GSK-3β activation. Furthermore, we examined whether c-Myc was involved in the anti-proliferative effect of DIF-1 using c-Myc–overexpressing cells and found that c-Myc was associated with the anti-proliferative effect of this compound. These results suggest that DIF-1 inhibits c-Myc expression by inhibiting promoter activity and inducing protein degradation via GSK-3β activation, resulting in the inhibition of cell proliferation. Since c-Myc seems to be profoundly involved in accelerated proliferation of various malignant tumors, DIF-1 may have a potential to develop into a novel anti-cancer agent.

【 授权许可】

Unknown