Differentiation-inducing factor-1 suppresses the expression of c-myc in the human cancer cell lines

Kentaro Jingushi, Toshihisa Nakamura, Fumi Takahashi-Yanaga, Etsuko Matsuzaki, Yutaka Watanabe, Tatsuya Yoshihara, Sachio Morimoto, Toshiyuki Sasaguri

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)103-109
Number of pages7
JournalJournal of Pharmacological Sciences
Volume121
Issue number2
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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