Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells
Polyphenols from olive oil are endowed with several biological activities. Chemical modifications have been recently applied to these compounds to improve their therapeutic activity in different pathological settings, including cancer. Herein, we describe the in vitro effects on multiple myeloma (MM...
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2021
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oai:doaj.org-article:1db0a636bd7048878db840cf0c79ad9e2021-11-11T17:06:50ZOleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells10.3390/ijms2221116391422-00671661-6596https://doaj.org/article/1db0a636bd7048878db840cf0c79ad9e2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11639https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Polyphenols from olive oil are endowed with several biological activities. Chemical modifications have been recently applied to these compounds to improve their therapeutic activity in different pathological settings, including cancer. Herein, we describe the in vitro effects on multiple myeloma (MM) cells of oleil hydroxytyrosol (HTOL), a synthetic fatty ester of natural hydroxytyrosol with oleic acid. HTOL reduced the viability of various human MM cell lines (HMCLs), even when co-cultured with bone marrow stromal cells, triggering ER stress, UPR and apoptosis, while it was not cytotoxic against healthy peripheral blood mononuclear cells or B lymphocytes. Whole-transcriptome profiling of HTOL-treated MM cells, coupled with protein expression analyses, indicate that HTOL antagonizes key survival pathways for malignant plasma cells, including the undruggable IRF4–c-MYC oncogenic axis. Accordingly, c-MYC gain- and loss-of-function strategies demonstrate that HTOL anti-tumor activity was, at least in part, due to c-MYC targeting. Taken together, these findings underscore the anti-MM potential of HTOL, providing the molecular framework for further investigation of HTOL-based treatments as novel anti-cancer agents.Katia TodoertiMaria Eugenia Gallo CantafioManuela OliverioGiada JuliCarmine RoccaRita CitraroPierfrancesco TassoneAntonio ProcopioGiovambattista De SarroAntonino NeriGiuseppe VigliettoNicola AmodioMDPI AGarticleexperimental therapeuticsmultiple myelomanatural anti-tumor agentsoleil hydroxytyrosolBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11639, p 11639 (2021) |
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| topic |
experimental therapeutics multiple myeloma natural anti-tumor agents oleil hydroxytyrosol Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
experimental therapeutics multiple myeloma natural anti-tumor agents oleil hydroxytyrosol Biology (General) QH301-705.5 Chemistry QD1-999 Katia Todoerti Maria Eugenia Gallo Cantafio Manuela Oliverio Giada Juli Carmine Rocca Rita Citraro Pierfrancesco Tassone Antonio Procopio Giovambattista De Sarro Antonino Neri Giuseppe Viglietto Nicola Amodio Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells |
| description |
Polyphenols from olive oil are endowed with several biological activities. Chemical modifications have been recently applied to these compounds to improve their therapeutic activity in different pathological settings, including cancer. Herein, we describe the in vitro effects on multiple myeloma (MM) cells of oleil hydroxytyrosol (HTOL), a synthetic fatty ester of natural hydroxytyrosol with oleic acid. HTOL reduced the viability of various human MM cell lines (HMCLs), even when co-cultured with bone marrow stromal cells, triggering ER stress, UPR and apoptosis, while it was not cytotoxic against healthy peripheral blood mononuclear cells or B lymphocytes. Whole-transcriptome profiling of HTOL-treated MM cells, coupled with protein expression analyses, indicate that HTOL antagonizes key survival pathways for malignant plasma cells, including the undruggable IRF4–c-MYC oncogenic axis. Accordingly, c-MYC gain- and loss-of-function strategies demonstrate that HTOL anti-tumor activity was, at least in part, due to c-MYC targeting. Taken together, these findings underscore the anti-MM potential of HTOL, providing the molecular framework for further investigation of HTOL-based treatments as novel anti-cancer agents. |
| format |
article |
| author |
Katia Todoerti Maria Eugenia Gallo Cantafio Manuela Oliverio Giada Juli Carmine Rocca Rita Citraro Pierfrancesco Tassone Antonio Procopio Giovambattista De Sarro Antonino Neri Giuseppe Viglietto Nicola Amodio |
| author_facet |
Katia Todoerti Maria Eugenia Gallo Cantafio Manuela Oliverio Giada Juli Carmine Rocca Rita Citraro Pierfrancesco Tassone Antonio Procopio Giovambattista De Sarro Antonino Neri Giuseppe Viglietto Nicola Amodio |
| author_sort |
Katia Todoerti |
| title |
Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells |
| title_short |
Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells |
| title_full |
Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells |
| title_fullStr |
Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells |
| title_full_unstemmed |
Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells |
| title_sort |
oleil hydroxytyrosol (htol) exerts anti-myeloma activity by antagonizing key survival pathways in malignant plasma cells |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/1db0a636bd7048878db840cf0c79ad9e |
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