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


Autoři: Wenbo Zhang aff001;  Cheng Hu aff001;  Xiaojie Wang aff001;  Shanshan Bai aff001;  Subing Cao aff002;  Margaret Kobelski aff002;  James R. Lambert aff003;  Jingkai Gu aff001;  Yang Zhan aff001
Působiště autorů: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, China aff001;  Department of Structural and Cellular Biology, Tulane Cancer Center, School of Medicine, Tulane University, New Orleans, Louisiana, United States of America aff002;  Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222812

Souhrn

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.

Klíčová slova:

Biology and life sciences – Cell biology – Physical sciences – Chemistry – Research and analysis methods – Cell processes – Anatomy – Medicine and health sciences – Urology – Oncology – Cancer treatment – Cancers and neoplasms – Cell death – Chemical elements – Immunologic techniques – Immunoassays – Enzyme-linked immunoassays – Apoptosis – Bioassays and physiological analysis – Microarrays – Exocrine glands – Cell proliferation – Genitourinary tract tumors – Prostate cancer – Prostate diseases – Prostate gland – Selenium


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