The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1625
JournalBiomedicines
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 2022

Keywords

  • bladder
  • CAPE
  • GDF15
  • maspin
  • NDRG1
  • Smad
  • TGFβ

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells'. Together they form a unique fingerprint.

Cite this