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–cMYC 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.

Oleil hydroxytyrosol (Htol) exerts anti-myeloma activity by antagonizing key survival pathways in malignant plasma cells / K. Todoerti, M.E. Gallo Cantafio, M. Oliverio, G. Juli, C. Rocca, R. Citraro, P. Tassone, A. Procopio, G. De Sarro, A. Neri, G. Viglietto, N. Amodio. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:21(2021), pp. 11639.1-11639.10. [10.3390/ijms222111639]

Oleil hydroxytyrosol (Htol) exerts anti-myeloma activity by antagonizing key survival pathways in malignant plasma cells

K. Todoerti
Primo
;
A. Neri;
2021

Abstract

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–cMYC 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.
Experimental therapeutics; Multiple myeloma; Natural anti-tumor agents; Oleil hydroxytyrosol
Settore MED/15 - Malattie del Sangue
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/885327
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