Cargando…

Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells

The growth inhibitory efficacy of methylseleninic acid (MSA) in prostate cancer cells has been documented extensively. However, our understanding of the immediate targets that are key to the growth inhibitory effects of MSA remains limited. Here, using multiple preclinical prostate cancer models, we...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Wenbo, Hu, Cheng, Wang, Xiaojie, Bai, Shanshan, Cao, Subing, Kobelski, Margaret, Lambert, James R., Gu, Jingkai, Zhan, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754141/
https://www.ncbi.nlm.nih.gov/pubmed/31539407
http://dx.doi.org/10.1371/journal.pone.0222812
_version_ 1783453029007097856
author Zhang, Wenbo
Hu, Cheng
Wang, Xiaojie
Bai, Shanshan
Cao, Subing
Kobelski, Margaret
Lambert, James R.
Gu, Jingkai
Zhan, Yang
author_facet Zhang, Wenbo
Hu, Cheng
Wang, Xiaojie
Bai, Shanshan
Cao, Subing
Kobelski, Margaret
Lambert, James R.
Gu, Jingkai
Zhan, Yang
author_sort Zhang, Wenbo
collection PubMed
description The growth inhibitory efficacy of methylseleninic acid (MSA) in prostate cancer cells has been documented extensively. However, our understanding of the immediate targets that are key to the growth inhibitory effects of MSA remains limited. Here, using multiple preclinical prostate cancer models, we demonstrated in vitro and in vivo that GDF15 is a most highly induced, immediate target of MSA. We further showed that knockdown of GDF15 mitigates MSA inhibition of cell proliferation and induction of apoptosis. Analysis of gene expression data from over 1000 primary and 200 metastatic prostate cancer samples revealed that GDF15 expression is decreased in metastatic prostate cancers compared to primary tumors and that lower GDF15 levels in primary tumors are associated with higher Gleason scores and shorter survival of the patients. Additionally, pathways that are negatively correlated with GDF15 levels in clinical samples are also negatively correlated with MSA treatment in cultured cells. Since most, if not all, of these pathways have been implicated in prostate cancer progression, suppressing their activities by inducing GDF15 is consistent with the anticancer effects of MSA in prostate cancer. Overall, this study provides support for GDF15 as an immediate target of MSA in prostate cancer cells.
format Online
Article
Text
id pubmed-6754141
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-67541412019-09-27 Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells Zhang, Wenbo Hu, Cheng Wang, Xiaojie Bai, Shanshan Cao, Subing Kobelski, Margaret Lambert, James R. Gu, Jingkai Zhan, Yang PLoS One Research Article The growth inhibitory efficacy of methylseleninic acid (MSA) in prostate cancer cells has been documented extensively. However, our understanding of the immediate targets that are key to the growth inhibitory effects of MSA remains limited. Here, using multiple preclinical prostate cancer models, we demonstrated in vitro and in vivo that GDF15 is a most highly induced, immediate target of MSA. We further showed that knockdown of GDF15 mitigates MSA inhibition of cell proliferation and induction of apoptosis. Analysis of gene expression data from over 1000 primary and 200 metastatic prostate cancer samples revealed that GDF15 expression is decreased in metastatic prostate cancers compared to primary tumors and that lower GDF15 levels in primary tumors are associated with higher Gleason scores and shorter survival of the patients. Additionally, pathways that are negatively correlated with GDF15 levels in clinical samples are also negatively correlated with MSA treatment in cultured cells. Since most, if not all, of these pathways have been implicated in prostate cancer progression, suppressing their activities by inducing GDF15 is consistent with the anticancer effects of MSA in prostate cancer. Overall, this study provides support for GDF15 as an immediate target of MSA in prostate cancer cells. Public Library of Science 2019-09-20 /pmc/articles/PMC6754141/ /pubmed/31539407 http://dx.doi.org/10.1371/journal.pone.0222812 Text en © 2019 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Wenbo
Hu, Cheng
Wang, Xiaojie
Bai, Shanshan
Cao, Subing
Kobelski, Margaret
Lambert, James R.
Gu, Jingkai
Zhan, Yang
Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells
title Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells
title_full Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells
title_fullStr Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells
title_full_unstemmed Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells
title_short Role of GDF15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells
title_sort role of gdf15 in methylseleninic acid-mediated inhibition of cell proliferation and induction of apoptosis in prostate cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754141/
https://www.ncbi.nlm.nih.gov/pubmed/31539407
http://dx.doi.org/10.1371/journal.pone.0222812
work_keys_str_mv AT zhangwenbo roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT hucheng roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT wangxiaojie roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT baishanshan roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT caosubing roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT kobelskimargaret roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT lambertjamesr roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT gujingkai roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells
AT zhanyang roleofgdf15inmethylseleninicacidmediatedinhibitionofcellproliferationandinductionofapoptosisinprostatecancercells