Heteronemin induces anti-Proliferation in cholangiocarcinoma cells via inhibiting TGF-β pathway

Hung Yun Lin, Shu Leei Tey, Yih Ho, Yung Tang Chin, Kuan Wang, Jacqueline Whang-Peng, Ya Jung Shih, Yi Ru Chen, Yung Ning Yang, Yu Cheng Chen, Yi Chang Liu, Heng Yuan Tang, Yu Chen SH Yang

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


A marine sesterterpenoid-type natural product, heteronemin, retains anticancer effects. In the current study, we investigate the antitumor mechanism of heteronemin in cholangiocarcinoma cells and further explore its molecular targets. Initially, heteronemin exhibited potent cytotoxic effects against cholangiocarcinoma HuccT1 and SSP-25 cells. In vitro, heteronemin altered the abilities of cell adhesion and cell migration in HuccT1 and SSP-25 cell lines. It repressed messenger ribonucleic acid (mRNA) expression levels of transforming growth factor (TGF)-β, mothers against decapentaplegic homolog (SMAD) and Myc,whose protein products play important roles in regulating cell growth, angiogenesis, and metastasis. In addition, heteronemin altered several signaling pathways. The results indicate that heteronemin was able to modulate cell adhesion, the expression of extracellular matrix (ECM) receptors, the TGF-β pathway, cell motility, the membrane integration, metastasis response, matrix metalloproteinase (MMP) remodeling, the regulation of metabolism, sprouting angiogenesis, transcription factors, and vasculogenesis in cholangiocarcinoma cell lines. The results also suggest that it activated multiple signal transduction pathways to induce an anti-proliferation effect and anti-metastasis in cholangiocarcinoma. In conclusion, heteronemin may be used as a potential medicine for anticancer therapy.

Original languageEnglish
Article number489
JournalMarine Drugs
Issue number12
Publication statusPublished - Dec 6 2018


  • Cholangiocarcinoma
  • Heteronemin
  • TGF-β pathway

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
  • Pharmaceutical Science


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