Destruxin B inhibits hepatocellular carcinoma cell growth through modulation of the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition

Thanh Tuan Huynh, Yerra Koteswara Rao, Wei Hwa Lee, Hsin An Chen, T. Do Quyen Le, David T W Tzeng, Liang Shun Wang, Alexander T H Wu, Yuh Feng Lin, Yew Min Tzeng, Chi-Tai Yeh

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The aberrant activation of Wnt/β-catenin signaling plays an important role in the carcinogenesis and progression of hepatocellular carcinoma (HCC). Therefore, the Wnt/β-catenin signaling molecules are attractive candidates for the development of targeted therapies for this disease. The present study showed that destruxin B (DB) inhibits the proliferation and induces the apoptosis of HCC cells by decreasing the protein expression of anti-apoptotic Bcl-2 and Bcl-xL and increasing the expression of the proapoptotic protein Bax. More importantly, DB also attenuates Wnt-signaling in HCC cells by downregulating β-catenin, Tcf4, and β-catenin/Tcf4 transcriptional activity, which results in the decreased expression of β-catenin target genes, such as cyclin D1, c-myc, and survivin. Furthermore, DB affects the migratory and invasive abilities of Sk-Hep1 cells through the suppression of markers of the epithelial-mesenchymal transition (EMT). A synergistic anti-proliferative and migratory effect was achieved using the combination of DB and sorafenib in Sk-Hep1 cells. In conclusion, DB acts as a novel Wnt/β-catenin inhibitor and reduces the aggressiveness and invasive potential of HCC by altering the cells' EMT status and mobility. DB in combination with sorafenib may be considered for future clinical use for the management of metastatic HCC.

Original languageEnglish
Pages (from-to)552-561
Number of pages10
JournalToxicology in Vitro
Volume28
Issue number4
DOIs
Publication statusPublished - Jun 2014

Fingerprint

Catenins
Wnt Signaling Pathway
Epithelial-Mesenchymal Transition
Cell growth
Hepatocellular Carcinoma
Modulation
Growth
Apoptosis Regulatory Proteins
Cyclin D1
destruxin B
Carcinogenesis
Proteins
Down-Regulation
Genes
Chemical activation
Apoptosis
Molecules

Keywords

  • Destruxin B
  • EMT
  • HCC
  • Metastasis
  • Sorafenib combination
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

Destruxin B inhibits hepatocellular carcinoma cell growth through modulation of the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition. / Huynh, Thanh Tuan; Rao, Yerra Koteswara; Lee, Wei Hwa; Chen, Hsin An; Le, T. Do Quyen; Tzeng, David T W; Wang, Liang Shun; Wu, Alexander T H; Lin, Yuh Feng; Tzeng, Yew Min; Yeh, Chi-Tai.

In: Toxicology in Vitro, Vol. 28, No. 4, 06.2014, p. 552-561.

Research output: Contribution to journalArticle

Huynh, Thanh Tuan ; Rao, Yerra Koteswara ; Lee, Wei Hwa ; Chen, Hsin An ; Le, T. Do Quyen ; Tzeng, David T W ; Wang, Liang Shun ; Wu, Alexander T H ; Lin, Yuh Feng ; Tzeng, Yew Min ; Yeh, Chi-Tai. / Destruxin B inhibits hepatocellular carcinoma cell growth through modulation of the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition. In: Toxicology in Vitro. 2014 ; Vol. 28, No. 4. pp. 552-561.
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