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Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells

The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention a...

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Autores principales: Katta, Shilpa, Srivastava, Arun, Thangapazham, Rajesh L., Rosner, Inger L., Cullen, Jennifer, Li, Hua, Sharad, Shashwat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801832/
https://www.ncbi.nlm.nih.gov/pubmed/31581661
http://dx.doi.org/10.3390/ijms20194891
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author Katta, Shilpa
Srivastava, Arun
Thangapazham, Rajesh L.
Rosner, Inger L.
Cullen, Jennifer
Li, Hua
Sharad, Shashwat
author_facet Katta, Shilpa
Srivastava, Arun
Thangapazham, Rajesh L.
Rosner, Inger L.
Cullen, Jennifer
Li, Hua
Sharad, Shashwat
author_sort Katta, Shilpa
collection PubMed
description The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention agents. Curcumin, a known chemo-preventive agent, was shown to inhibit prostate cancer cell growth. This study aimed to unravel the inhibitory effect of curcumin in prostate cancer through analyzing the alterations of expressions of curcumin targeting genes clusters in androgen-dependent LNCaP cells and androgen-independent metastatic C4-2B cells. Hierarchical clustering showed the highest number of differentially expressed genes at 12 h post treatment in both cells, suggesting that the androgen-dependent/independent manner of curcumin impacts on prostate cancer cells. Evaluation of significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-β), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited, and Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment. The short term (3–24 h) and long term (48 h) effect of curcumin treatment revealed 31 and four genes modulated in both cell lines. TGF-β signaling, including the androgen/TGF-β inhibitor Prostate transmembrane protein androgen-induced 1 (PMEPA1), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. This study established, for the first time, novel gene-networks and signaling pathways confirming the chemo-preventive and cancer-growth inhibitory nature of curcumin as a natural anti-prostate cancer compound.
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spelling pubmed-68018322019-10-31 Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells Katta, Shilpa Srivastava, Arun Thangapazham, Rajesh L. Rosner, Inger L. Cullen, Jennifer Li, Hua Sharad, Shashwat Int J Mol Sci Article The androgen receptor is one of the key targets for prostate cancer treatment. Despite its less satisfactory effects, chemotherapy is the most common treatment option for metastatic and/or castration-resistant patients. There are constant needs for novel anti-prostate cancer therapeutic/prevention agents. Curcumin, a known chemo-preventive agent, was shown to inhibit prostate cancer cell growth. This study aimed to unravel the inhibitory effect of curcumin in prostate cancer through analyzing the alterations of expressions of curcumin targeting genes clusters in androgen-dependent LNCaP cells and androgen-independent metastatic C4-2B cells. Hierarchical clustering showed the highest number of differentially expressed genes at 12 h post treatment in both cells, suggesting that the androgen-dependent/independent manner of curcumin impacts on prostate cancer cells. Evaluation of significantly regulated top canonical pathways highlighted that Transforming growth factor beta (TGF-β), Wingless-related integration site (Wnt), Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin (PIK3/AKT(PKB)/mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling were primarily inhibited, and Phosphatase and tensin homolog (PTEN) dependent cell cycle arrest and apoptosis pathways were elevated with curcumin treatment. The short term (3–24 h) and long term (48 h) effect of curcumin treatment revealed 31 and four genes modulated in both cell lines. TGF-β signaling, including the androgen/TGF-β inhibitor Prostate transmembrane protein androgen-induced 1 (PMEPA1), was the only pathway impacted by curcumin treatment after 48 h. Our findings also established that MYC Proto-Oncogene, basic helix-loop-helix (bHLH) Transcription Factor (MYC) signaling was down-regulated in curcumin-treated cell lines. This study established, for the first time, novel gene-networks and signaling pathways confirming the chemo-preventive and cancer-growth inhibitory nature of curcumin as a natural anti-prostate cancer compound. MDPI 2019-10-02 /pmc/articles/PMC6801832/ /pubmed/31581661 http://dx.doi.org/10.3390/ijms20194891 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Katta, Shilpa
Srivastava, Arun
Thangapazham, Rajesh L.
Rosner, Inger L.
Cullen, Jennifer
Li, Hua
Sharad, Shashwat
Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells
title Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells
title_full Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells
title_fullStr Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells
title_full_unstemmed Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells
title_short Curcumin-Gene Expression Response in Hormone Dependent and Independent Metastatic Prostate Cancer Cells
title_sort curcumin-gene expression response in hormone dependent and independent metastatic prostate cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801832/
https://www.ncbi.nlm.nih.gov/pubmed/31581661
http://dx.doi.org/10.3390/ijms20194891
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