Next Article in Journal
Comparison of Hydrogels Based on Commercial Chitosan and Beetosan® Containing Nanosilver
Next Article in Special Issue
Role of UDP-Glucuronosyltransferase 1A1 in the Metabolism and Pharmacokinetics of Silymarin Flavonolignans in Patients with HCV and NAFLD
Previous Article in Journal
How Does Thymine DNA Survive Ultrafast Dimerization Damage?
Previous Article in Special Issue
Efficacy of Pre- and Post-Treatment by Topical Formulations Containing Dissolved and Suspended Silybum marianum against UVB-Induced Oxidative Stress in Guinea Pig and on HaCaT Keratinocytes
Open AccessArticle

A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma

1
Department of Molecular Biology and Genetics, Democritus University of Thrace, University Campus, Dragana, 68100 Alexandroupolis, Greece
2
Redox Biology Center, School of Veterinary Medicine & Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA
3
Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK
4
Department of Pharmaceutical Sciences, College of Science & Technology, Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, Durham, NC 27707, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Tung-Hu Tsai
Molecules 2017, 22(1), 62; https://doi.org/10.3390/molecules22010062
Received: 30 November 2016 / Accepted: 22 December 2016 / Published: 31 December 2016
(This article belongs to the Special Issue Silymarin)
Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR). Furthermore immunoblot and immunofluorescence analysis revealed that silibinin-mediated reduction of EZH2 levels was accompanied by an increase in trimethylation of histone H3 on lysine (Κ)-27 residue (H3K27me3) levels and that such response was, in part, dependent on decreased expression levels of phosphorylated Akt (ser473) (pAkt) and phosphorylated EZH2 (ser21) (pEZH2). Additionally silibinin exerted other epigenetic effects involving an increase in total DNA methyltransferase (DNMT) activity while it decreased histone deacetylases 1-2 (HDACs1-2) expression levels. We conclude that silibinin induces epigenetic alterations in human prostate cancer cells, suggesting that subsequent disruptions of central processes in chromatin conformation may account for some of its diverse anticancer effects. View Full-Text
Keywords: silibinin; EZH2; PRC2; histone methylation; H3K27me3; DNMT; HDAC; epigenetics; prostate cancer silibinin; EZH2; PRC2; histone methylation; H3K27me3; DNMT; HDAC; epigenetics; prostate cancer
Show Figures

Figure 1

MDPI and ACS Style

Anestopoulos, I.; Sfakianos, A.P.; Franco, R.; Chlichlia, K.; Panayiotidis, M.I.; Kroll, D.J.; Pappa, A. A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma. Molecules 2017, 22, 62.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop