Antcin-A Modulates Epithelial-to-Mesenchymal Transition and Inhibits Migratory and Invasive Potentials of Human Breast Cancer Cells via p53-Mediated miR-200c Activation

K. J. Senthil Kumar; M. Gokila Vani; Han-Wen Hsieh; Chin-Chung Lin; Sheng-Yang Wang

doi:10.1055/a-0942-2087

Planta Medica, Table of Contents

Planta Med 2019; 85(09/10): 755-765
DOI: 10.1055/a-0942-2087

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Antcin-A Modulates Epithelial-to-Mesenchymal Transition and Inhibits Migratory and Invasive Potentials of Human Breast Cancer Cells via p53-Mediated miR-200c Activation

K. J. Senthil Kumar

¹Department of Forestry, National Chung Hsing University, Taichung, Taiwan

,

M. Gokila Vani

¹Department of Forestry, National Chung Hsing University, Taichung, Taiwan

,

Han-Wen Hsieh

²Taiwan Leader Biotech Company, Taipei, Taiwan

,

Chin-Chung Lin

²Taiwan Leader Biotech Company, Taipei, Taiwan

,

Sheng-Yang Wang

¹Department of Forestry, National Chung Hsing University, Taichung, Taiwan

³Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan

› Author Affiliations

Abstract

Antcin-A (ATA) is a steroid-like phytochemical isolated from the fruiting bodies of a precious edible mushroom Antrodia cinnamomea. We previously showed that ATA has strong anti-inflammatory and anti-tumor effects; however, other possible bioactivities of this unique compound remain unexplored. In the present study, we aimed to investigate the modulation of epithelial-to-mesenchymal transition (EMT), anti-migration, and anti-invasive potential of ATA against human breast cancer cells in vitro. Human breast cancer cell lines, MCF-7 and MDA-MB-231, were incubated with ATA for 24 h. Wound healing, trans-well invasion, western blot, q-PCR, F-actin staining, and immunofluorescence assays were performed. We found that treatment with ATA significantly blocked EMT processes, as evidenced by upregulation of epithelial markers (E-cadherin and occludin) and downregulation of mesenchymal markers (N-cadherin and vimentin) via suppression of their transcriptional repressor ZEB1. Next, we found that ATA could induce miR-200c, which is a known player of ZEB1 repression. Further investigations revealed that ATA-mediated induction of miR-200c is associated with transcriptional activation of p53, as confirmed by the fact that ATA failed to induce miR-200c or suppress ZEB1 activity in p53 inhibited cells. Further in vitro wound healing and trans-well invasion assays support that ATA could inhibit migratory and invasive potentials of breast cancer cells, and the effect was likely associated with induced phenotypic modulation. Taken together, the present study suggests that antcin-A could be a lead phyto-agent for the development of anti-metastatic drug for breast cancer treatment.

Key words

antcin-A - Antrodia cinnamomea - Fomitopsidaceae - breast cancer - epithelial-to-mesenchymal transition - miR-200c - ZEB1 - p53

Full Text

References

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