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Anti-tumor Activity and Epigenetic Impact of the Polyphenol Oleacein in Multiple Myeloma
- Source :
- Cancers, Vol 11, Iss 7, p 990 (2019), Cancers, Volume 11, Issue 7, Cancers (Basel) 11 (2019): 990. doi:10.3390/cancers11070990., info:cnr-pdr/source/autori:Giada Juli 1, Manuela Oliverio 2, Dina Bellizzi 3, Maria Eugenia Gallo Cantafio 1,Katia Grillone 1, Giuseppe Passarino 3, Carmela Colica 4, Monica Nardi 2, Marco Rossi 1,Antonio Procopio 2, Pierosandro Tagliaferri 1, Pierfrancesco Tassone 1 and Nicola Amodio 1/titolo:Anti-tumor Activity and Epigenetic Impact of the Polyphenol Oleacein in Multiple Myeloma./doi:10.3390%2Fcancers11070990./rivista:Cancers (Basel)/anno:2019/pagina_da:990/pagina_a:/intervallo_pagine:990/volume:11
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Olive oil contains different biologically active polyphenols, among which oleacein, the most abundant secoiridoid, has recently emerged for its beneficial properties in various disease contexts. By using in vitro models of human multiple myeloma (MM), we here investigated the anti-tumor potential of oleacein and the underlying bio-molecular sequelae. Within a low micromolar range, oleacein reduced the viability of MM primary samples and cell lines even in the presence of bone marrow stromal cells (BMSCs), while sparing healthy peripheral blood mononuclear cells. We also demonstrated that oleacein inhibited MM cell clonogenicity, prompted cell cycle blockade and triggered apoptosis. We evaluated the epigenetic impact of oleacein on MM cells, and observed dose-dependent accumulation of both acetylated histones and &alpha<br />tubulin, along with down-regulation of several class I/II histone deacetylases (HDACs) both at the mRNA and protein level, providing evidence of the HDAC inhibitory activity of this compound<br />conversely, no effect on global DNA methylation was found. Mechanistically, HDACs inhibition by oleacein was associated with down-regulation of Sp1, the major transactivator of HDACs promoter, via Caspase 8 activation. Of potential translational significance, oleacein synergistically enhanced the in vitro anti-MM activity of the proteasome inhibitor carfilzomib. Altogether, these results indicate that oleacein is endowed with HDAC inhibitory properties, which associate with significant anti-MM activity both as single agent or in combination with carfilzomib. These findings may pave the way to novel potential anti-MM epi-therapeutic approaches based on natural agents.
- Subjects :
- Cancer Research
Stromal cell
Chemistry
Cell
Biological activity
Cell cycle
Caspase 8
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Carfilzomib
lcsh:RC254-282
Article
HDAC
experimental therapeutics
multiple myeloma
oleacein
chemistry.chemical_compound
medicine.anatomical_structure
Oncology
Apoptosis
Proteasome inhibitor
medicine
Cancer research
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....7b9c71dda10b6e13bf732cd1c5f4a1f9