The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells
Growth differentiation factor 15 (GDF15) is known as a TGFβ-like cytokine acting on the TGFβ receptor to modulate target genes. GDF15 is regarded as a tumor suppressor gene in the human bladder and the caffeic acid phenethyl ester (CAPE) induces GDF15 expression to inhibit the tumor growth in vitro...
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MDPI AG
2022-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/7/1625 |
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| author | Chen-Pang Hou Ke-Hung Tsui Syue-Ting Chen Kang-Shuo Chang Hsin-Ching Sung Shu-Yuan Hsu Yu-Hsiang Lin Tsui-Hsia Feng Horng-Heng Juang |
| author_facet | Chen-Pang Hou Ke-Hung Tsui Syue-Ting Chen Kang-Shuo Chang Hsin-Ching Sung Shu-Yuan Hsu Yu-Hsiang Lin Tsui-Hsia Feng Horng-Heng Juang |
| author_sort | Chen-Pang Hou |
| collection | DOAJ |
| description | Growth differentiation factor 15 (GDF15) is known as a TGFβ-like cytokine acting on the TGFβ receptor to modulate target genes. GDF15 is regarded as a tumor suppressor gene in the human bladder and the caffeic acid phenethyl ester (CAPE) induces GDF15 expression to inhibit the tumor growth in vitro and in vivo. However, the interactions among GDF15, CAPE, and TGFβ/Smads signaling in the human bladder carcinoma cells remain unexplored. Results revealed that TGFβ downregulated the expression of GDF15 via the activation of Smad 2/3 and Smad 1/5. Induction of GDF15 on its downstream genes, NDRG1 and maspin, is dependent on the TGFβ/Smad pathways. Moreover, TGFβ blocked the CAPE-inducing expressions of GDF15, maspin, and NDRG1. Pretreatment of TGF receptor kinase inhibitor not only blocked the activation of TGFβ but also attenuated the activation of GDF15 on the expressions of maspin and NDRG1. The CAPE treatment attenuated the activation of TGFβ on cell proliferation and invasion. Our findings indicate that TGFβ downregulated the expressions of GDF15, maspin, and NDRG1 via TGFβ/Smad signaling. Whereas, CAPE acts as an antagonist on TGFβ/Smad signaling to block the effect of TGFβ on the GDF15 expression and cell proliferation and invasion in bladder carcinoma cells. |
| first_indexed | 2024-03-09T03:40:51Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T03:40:51Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d1b276a7fc00418eadf88810c4d2bb5f2023-12-03T14:42:04ZengMDPI AGBiomedicines2227-90592022-07-01107162510.3390/biomedicines10071625The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma CellsChen-Pang Hou0Ke-Hung Tsui1Syue-Ting Chen2Kang-Shuo Chang3Hsin-Ching Sung4Shu-Yuan Hsu5Yu-Hsiang Lin6Tsui-Hsia Feng7Horng-Heng Juang8Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 33302, TaiwanDepartment of Urology, Shuang Ho Hospital, New Taipei City 235041, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 33302, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 33302, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 33302, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 33302, TaiwanDepartment of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Taoyuan 33302, TaiwanSchool of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 33302, TaiwanDepartment of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Taoyuan 33302, TaiwanGrowth differentiation factor 15 (GDF15) is known as a TGFβ-like cytokine acting on the TGFβ receptor to modulate target genes. GDF15 is regarded as a tumor suppressor gene in the human bladder and the caffeic acid phenethyl ester (CAPE) induces GDF15 expression to inhibit the tumor growth in vitro and in vivo. However, the interactions among GDF15, CAPE, and TGFβ/Smads signaling in the human bladder carcinoma cells remain unexplored. Results revealed that TGFβ downregulated the expression of GDF15 via the activation of Smad 2/3 and Smad 1/5. Induction of GDF15 on its downstream genes, NDRG1 and maspin, is dependent on the TGFβ/Smad pathways. Moreover, TGFβ blocked the CAPE-inducing expressions of GDF15, maspin, and NDRG1. Pretreatment of TGF receptor kinase inhibitor not only blocked the activation of TGFβ but also attenuated the activation of GDF15 on the expressions of maspin and NDRG1. The CAPE treatment attenuated the activation of TGFβ on cell proliferation and invasion. Our findings indicate that TGFβ downregulated the expressions of GDF15, maspin, and NDRG1 via TGFβ/Smad signaling. Whereas, CAPE acts as an antagonist on TGFβ/Smad signaling to block the effect of TGFβ on the GDF15 expression and cell proliferation and invasion in bladder carcinoma cells.https://www.mdpi.com/2227-9059/10/7/1625bladderTGFβSmadCAPEGDF15maspin |
| spellingShingle | Chen-Pang Hou Ke-Hung Tsui Syue-Ting Chen Kang-Shuo Chang Hsin-Ching Sung Shu-Yuan Hsu Yu-Hsiang Lin Tsui-Hsia Feng Horng-Heng Juang The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells Biomedicines bladder TGFβ Smad CAPE GDF15 maspin |
| title | The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells |
| title_full | The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells |
| title_fullStr | The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells |
| title_full_unstemmed | The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells |
| title_short | The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells |
| title_sort | upregulation of caffeic acid phenethyl ester on growth differentiation factor 15 inhibits transforming growth factor β smad signaling in bladder carcinoma cells |
| topic | bladder TGFβ Smad CAPE GDF15 maspin |
| url | https://www.mdpi.com/2227-9059/10/7/1625 |
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