Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319303858 |
| _version_ | 1818039289920880640 |
|---|---|
| author | Kentaro Jingushi Toshihisa Nakamura Fumi Takahashi-Yanaga Etsuko Matsuzaki Yutaka Watanabe Tatsuya Yoshihara Sachio Morimoto Toshiyuki Sasaguri |
| author_facet | Kentaro Jingushi Toshihisa Nakamura Fumi Takahashi-Yanaga Etsuko Matsuzaki Yutaka Watanabe Tatsuya Yoshihara Sachio Morimoto Toshiyuki Sasaguri |
| author_sort | Kentaro Jingushi |
| collection | DOAJ |
| description | 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. Keywords:: c-Myc, Wnt/β-catenin signaling pathway, colon cancer cell, differentiation-inducing factor-1, glycogen synthase kinase-3β |
| first_indexed | 2024-12-10T07:56:16Z |
| format | Article |
| id | doaj.art-90601118b2654fb192711adffd7e4591 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T07:56:16Z |
| publishDate | 2013-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-90601118b2654fb192711adffd7e45912022-12-22T01:56:53ZengElsevierJournal of Pharmacological Sciences1347-86132013-01-011212103109Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell LinesKentaro Jingushi0Toshihisa Nakamura1Fumi Takahashi-Yanaga2Etsuko Matsuzaki3Yutaka Watanabe4Tatsuya Yoshihara5Sachio Morimoto6Toshiyuki Sasaguri7Department of Clinical Pharmacology, Faculty of Medical Sciences, Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan; Corresponding author. yanaga@clipharm.med.kyushu-u.ac.jpPeriodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama 790-8577, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Periodontology Section, Division of Oral Rehabilitation, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, JapanDifferentiation-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. Keywords:: c-Myc, Wnt/β-catenin signaling pathway, colon cancer cell, differentiation-inducing factor-1, glycogen synthase kinase-3βhttp://www.sciencedirect.com/science/article/pii/S1347861319303858 |
| spellingShingle | Kentaro Jingushi Toshihisa Nakamura Fumi Takahashi-Yanaga Etsuko Matsuzaki Yutaka Watanabe Tatsuya Yoshihara Sachio Morimoto Toshiyuki Sasaguri Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines Journal of Pharmacological Sciences |
| title | Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines |
| title_full | Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines |
| title_fullStr | Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines |
| title_full_unstemmed | Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines |
| title_short | Differentiation-Inducing Factor-1 Suppresses the Expression of c-Myc in the Human Cancer Cell Lines |
| title_sort | differentiation inducing factor 1 suppresses the expression of c myc in the human cancer cell lines |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319303858 |
| work_keys_str_mv | AT kentarojingushi differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines AT toshihisanakamura differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines AT fumitakahashiyanaga differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines AT etsukomatsuzaki differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines AT yutakawatanabe differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines AT tatsuyayoshihara differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines AT sachiomorimoto differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines AT toshiyukisasaguri differentiationinducingfactor1suppressestheexpressionofcmycinthehumancancercelllines |