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 journalArticle

11 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 - Feb 26 2013

Fingerprint

Cell Line
Glycogen Synthase Kinase 3
Neoplasms
Proto-Oncogene Proteins c-myc
Catenins
Wnt Signaling Pathway
Proteolysis
1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone
Proteasome Inhibitors
Dictyostelium
Colonic Neoplasms
Binding Sites
Cell Proliferation
Messenger RNA
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Differentiation-inducing factor-1 suppresses the expression of c-myc in the human cancer cell lines. / Jingushi, Kentaro; Nakamura, Toshihisa; Takahashi-Yanaga, Fumi; Matsuzaki, Etsuko; Watanabe, Yutaka; Yoshihara, Tatsuya; Morimoto, Sachio; Sasaguri, Toshiyuki.

In: Journal of Pharmacological Sciences, Vol. 121, No. 2, 26.02.2013, p. 103-109.

Research output: Contribution to journalArticle

Jingushi, K, Nakamura, T, Takahashi-Yanaga, F, Matsuzaki, E, Watanabe, Y, Yoshihara, T, Morimoto, S & Sasaguri, T 2013, 'Differentiation-inducing factor-1 suppresses the expression of c-myc in the human cancer cell lines', Journal of Pharmacological Sciences, vol. 121, no. 2, pp. 103-109. https://doi.org/10.1254/jphs.12204FP
Jingushi K, Nakamura T, Takahashi-Yanaga F, Matsuzaki E, Watanabe Y, Yoshihara T et al. Differentiation-inducing factor-1 suppresses the expression of c-myc in the human cancer cell lines. Journal of Pharmacological Sciences. 2013 Feb 26;121(2):103-109. https://doi.org/10.1254/jphs.12204FP
Jingushi, Kentaro ; Nakamura, Toshihisa ; Takahashi-Yanaga, Fumi ; Matsuzaki, Etsuko ; Watanabe, Yutaka ; Yoshihara, Tatsuya ; Morimoto, Sachio ; Sasaguri, Toshiyuki. / Differentiation-inducing factor-1 suppresses the expression of c-myc in the human cancer cell lines. In: Journal of Pharmacological Sciences. 2013 ; Vol. 121, No. 2. pp. 103-109.
@article{81d5cb3b72fe4d13bc49cc4e7bf1a52f,
title = "Differentiation-inducing factor-1 suppresses the expression of c-myc in the human cancer cell lines",
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.",
author = "Kentaro Jingushi and Toshihisa Nakamura and Fumi Takahashi-Yanaga and Etsuko Matsuzaki and Yutaka Watanabe and Tatsuya Yoshihara and Sachio Morimoto and Toshiyuki Sasaguri",
year = "2013",
month = "2",
day = "26",
doi = "10.1254/jphs.12204FP",
language = "English",
volume = "121",
pages = "103--109",
journal = "Journal of Pharmacological Sciences",
issn = "1347-8613",
publisher = "Japanese Pharmacological Society",
number = "2",

}

TY - JOUR

T1 - Differentiation-inducing factor-1 suppresses the expression of c-myc in the human cancer cell lines

AU - Jingushi, Kentaro

AU - Nakamura, Toshihisa

AU - Takahashi-Yanaga, Fumi

AU - Matsuzaki, Etsuko

AU - Watanabe, Yutaka

AU - Yoshihara, Tatsuya

AU - Morimoto, Sachio

AU - Sasaguri, Toshiyuki

PY - 2013/2/26

Y1 - 2013/2/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84874156223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874156223&partnerID=8YFLogxK

U2 - 10.1254/jphs.12204FP

DO - 10.1254/jphs.12204FP

M3 - Article

C2 - 23357875

AN - SCOPUS:84874156223

VL - 121

SP - 103

EP - 109

JO - Journal of Pharmacological Sciences

JF - Journal of Pharmacological Sciences

SN - 1347-8613

IS - 2

ER -