Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line

Abstract Enzalutamide (ENZ) is an important drug used to treat castration-resistant prostate cancer (CRPC), which inhibits androgen receptor (AR) signaling. Previous study showed that 3,3′-diindolylmethane (DIM) is an AR antagonist that also inhibits Wnt signaling and epithelial-mesenchymal transiti...

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Autores principales: Chih-Wei Tsao, Jia-Sin Li, Ya-Wen Lin, Sheng-Tang Wu, Tai-Lung Cha, Chin-Yu Liu
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:a801bc9d8c684eddbab310572a29d9202021-12-02T14:01:20ZRegulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line10.1038/s41598-020-80519-32045-2322https://doaj.org/article/a801bc9d8c684eddbab310572a29d9202021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80519-3https://doaj.org/toc/2045-2322Abstract Enzalutamide (ENZ) is an important drug used to treat castration-resistant prostate cancer (CRPC), which inhibits androgen receptor (AR) signaling. Previous study showed that 3,3′-diindolylmethane (DIM) is an AR antagonist that also inhibits Wnt signaling and epithelial-mesenchymal transition (EMT). To investigate whether combined treatment with ENZ and DIM can overcome ENZ resistance by regulating Wnt signaling to inhibit AR signaling and EMT in ENZ-resistant prostate cancer cells, 22Rv1 cells were cultured in normal medium and treated with ENZ, DIM, and DIM with ENZ. Exposure of ENZ-resistant cells to both DIM and ENZ significantly inhibited cell proliferation without cytotoxicity and invasion in comparison with the control. DIM significantly increased the E-cadherin expression and inhibited the expressions of Vimentin and Fibronectin, subsequently inhibiting EMT. Co-treatment with ENZ and DIM significantly increased the expressions of GSK3β and APC and decreased the β-catenin protein expression, causing inhibition of Wnt signaling and AR expression, it also significantly decreased the AR-v7 expression and down-regulated AR signaling. Via suppression of Wnt and AR signaling, co-treatment increased the E-cadherin and decreased the Vimentin and Fibronectin RNA and protein expressions, then inhibited EMT. Co-treatment with DIM and ENZ regulated Wnt signaling to reduce not only the AR expression, but also the AR-v7 expression, indicating suppression of EMT that inhibits cancer cell proliferation, invasion and migration to ameliorate ENZ resistance.Chih-Wei TsaoJia-Sin LiYa-Wen LinSheng-Tang WuTai-Lung ChaChin-Yu LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Chih-Wei Tsao
Jia-Sin Li
Ya-Wen Lin
Sheng-Tang Wu
Tai-Lung Cha
Chin-Yu Liu
Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line
description Abstract Enzalutamide (ENZ) is an important drug used to treat castration-resistant prostate cancer (CRPC), which inhibits androgen receptor (AR) signaling. Previous study showed that 3,3′-diindolylmethane (DIM) is an AR antagonist that also inhibits Wnt signaling and epithelial-mesenchymal transition (EMT). To investigate whether combined treatment with ENZ and DIM can overcome ENZ resistance by regulating Wnt signaling to inhibit AR signaling and EMT in ENZ-resistant prostate cancer cells, 22Rv1 cells were cultured in normal medium and treated with ENZ, DIM, and DIM with ENZ. Exposure of ENZ-resistant cells to both DIM and ENZ significantly inhibited cell proliferation without cytotoxicity and invasion in comparison with the control. DIM significantly increased the E-cadherin expression and inhibited the expressions of Vimentin and Fibronectin, subsequently inhibiting EMT. Co-treatment with ENZ and DIM significantly increased the expressions of GSK3β and APC and decreased the β-catenin protein expression, causing inhibition of Wnt signaling and AR expression, it also significantly decreased the AR-v7 expression and down-regulated AR signaling. Via suppression of Wnt and AR signaling, co-treatment increased the E-cadherin and decreased the Vimentin and Fibronectin RNA and protein expressions, then inhibited EMT. Co-treatment with DIM and ENZ regulated Wnt signaling to reduce not only the AR expression, but also the AR-v7 expression, indicating suppression of EMT that inhibits cancer cell proliferation, invasion and migration to ameliorate ENZ resistance.
format article
author Chih-Wei Tsao
Jia-Sin Li
Ya-Wen Lin
Sheng-Tang Wu
Tai-Lung Cha
Chin-Yu Liu
author_facet Chih-Wei Tsao
Jia-Sin Li
Ya-Wen Lin
Sheng-Tang Wu
Tai-Lung Cha
Chin-Yu Liu
author_sort Chih-Wei Tsao
title Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line
title_short Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line
title_full Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line
title_fullStr Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line
title_full_unstemmed Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line
title_sort regulation of carcinogenesis and mediation through wnt/β-catenin signaling by 3,3′-diindolylmethane in an enzalutamide-resistant prostate cancer cell line
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/a801bc9d8c684eddbab310572a29d920
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