Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

2-(4-Benzyloxy-3-Methoxyphenyl)-5-(Carbethoxyethylene)-7-Methoxy-Benzofuran, a Benzofuran Derivative, Suppresses Metastasis Effects in P53-Mutant Hepatocellular Carcinoma Cells

Version 1 : Received: 29 May 2023 / Approved: 30 May 2023 / Online: 30 May 2023 (08:21:26 CEST)

A peer-reviewed article of this Preprint also exists.

Tseng, T.-H.; Shao, Y.-C.; Lee, Y.-J.; Lee, H.-J. 2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran, a Benzofuran Derivative, Suppresses Metastasis Effects in P53-Mutant Hepatocellular Carcinoma Cells. Biomedicines 2023, 11, 2027. Tseng, T.-H.; Shao, Y.-C.; Lee, Y.-J.; Lee, H.-J. 2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran, a Benzofuran Derivative, Suppresses Metastasis Effects in P53-Mutant Hepatocellular Carcinoma Cells. Biomedicines 2023, 11, 2027.

Abstract

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran (BMBF), a benzofuran derivative, is an intermediate found in the process of total synthesis of ailanthoidol. Benzofuran derivatives are a class of compounds that possess various biological and pharmacological activities. The present study explored the anti-metastasis effects in hepatocellular carcinoma (HCC). Our preliminary findings indicate that BMBF suppresses the proliferation and changes the morphology of Huh7, an HCC cell line with a mutated p53 gene (Y220C). According to scratching motility assay, noncytotoxic concentrations of BMBF significantly inhibited the motility and migration in Huh7 cells. BMBF upregulated the expression of E-cadherin and downregulated the expression of vimentin, Slug, and MMP9, which are associated with epithelial-mesenchymal-transition (EMT) and metastasis in Huh7 cells. BMBF decreased the expression of integrin α7 and deactivated its downstream signal FAK/AKT and inhibited p53 protein levels. Cell transfection with p53 siRNA resulted in prevention of cell invasion because of the reduced expression of integrin α7, Slug, and MMP-9 in Huh7 cells. BMBF had anti-metastatic effects in PLC/PRF/5, an HCC cell line with R249S, a mutated p53 gene. Our findings indicate that BMBF has anti-metastatic effects in that it downregulates p53 and mediates the suppression of integrin α7, EMT, and MMP-9 in HCC cells with mutated p53 gene.

Keywords

Benzofuran; Ailanthoidol; p53; Hepatocellular carcinoma; Epithelia-mesenchymal transition; Metastasis

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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