Suppression of multiple myeloma by mitochondrial targeting

Abstract Treatment of multiple myeloma (MM) aims at inducing cell apoptosis by surpassing the limited capacity of MM cells to cope with oxidative stress. MM cell survival may further be suppressed by limiting cellular cholesterol. Long-chain fatty acid analogs of the MEDICA series promote mitochondr...

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Autores principales:	Yana Aisen, Moshe E. Gatt, Rachel Hertz, Elia Smeir, Jacob Bar-Tana
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/48da890086fd45d8856e963201073334
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spelling	oai:doaj.org-article:48da890086fd45d8856e9632010733342021-12-02T13:31:11ZSuppression of multiple myeloma by mitochondrial targeting10.1038/s41598-021-83829-22045-2322https://doaj.org/article/48da890086fd45d8856e9632010733342021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83829-2https://doaj.org/toc/2045-2322Abstract Treatment of multiple myeloma (MM) aims at inducing cell apoptosis by surpassing the limited capacity of MM cells to cope with oxidative stress. MM cell survival may further be suppressed by limiting cellular cholesterol. Long-chain fatty acid analogs of the MEDICA series promote mitochondrial stress and inhibit cholesterol biosynthesis, thus prompting us to verify their efficacy and mode-of-action in suppressing MM cell survival, in comparison to bortezomib. MEDICA analog is shown here to effectively suppress survival of MM cells, and to inhibit growth of MM xenograft. Suppression of MM cell survival by MEDICA is accompanied by inhibition of the STAT3, MAPK and the mTORC1 transduction pathways due to mitochondrial oxidative stress. MEDICA-induced oxidative stress is abrogated by added exogenous cholesterol. Suppression of MM cell survival by bortezomib is similarly driven by bortezomib-induced oxidative stress, being abrogated by added cholesterol. In line with that, the time-to-best-response of MM patients to bortezomib-based treatment protocols is shown to be positively correlated with their plasma cholesterol level. MEDICA profile may indicate novel therapeutic potential in the management of MM.Yana AisenMoshe E. GattRachel HertzElia SmeirJacob Bar-TanaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yana Aisen Moshe E. Gatt Rachel Hertz Elia Smeir Jacob Bar-Tana Suppression of multiple myeloma by mitochondrial targeting
description	Abstract Treatment of multiple myeloma (MM) aims at inducing cell apoptosis by surpassing the limited capacity of MM cells to cope with oxidative stress. MM cell survival may further be suppressed by limiting cellular cholesterol. Long-chain fatty acid analogs of the MEDICA series promote mitochondrial stress and inhibit cholesterol biosynthesis, thus prompting us to verify their efficacy and mode-of-action in suppressing MM cell survival, in comparison to bortezomib. MEDICA analog is shown here to effectively suppress survival of MM cells, and to inhibit growth of MM xenograft. Suppression of MM cell survival by MEDICA is accompanied by inhibition of the STAT3, MAPK and the mTORC1 transduction pathways due to mitochondrial oxidative stress. MEDICA-induced oxidative stress is abrogated by added exogenous cholesterol. Suppression of MM cell survival by bortezomib is similarly driven by bortezomib-induced oxidative stress, being abrogated by added cholesterol. In line with that, the time-to-best-response of MM patients to bortezomib-based treatment protocols is shown to be positively correlated with their plasma cholesterol level. MEDICA profile may indicate novel therapeutic potential in the management of MM.
format	article
author	Yana Aisen Moshe E. Gatt Rachel Hertz Elia Smeir Jacob Bar-Tana
author_facet	Yana Aisen Moshe E. Gatt Rachel Hertz Elia Smeir Jacob Bar-Tana
author_sort	Yana Aisen
title	Suppression of multiple myeloma by mitochondrial targeting
title_short	Suppression of multiple myeloma by mitochondrial targeting
title_full	Suppression of multiple myeloma by mitochondrial targeting
title_fullStr	Suppression of multiple myeloma by mitochondrial targeting
title_full_unstemmed	Suppression of multiple myeloma by mitochondrial targeting
title_sort	suppression of multiple myeloma by mitochondrial targeting
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/48da890086fd45d8856e963201073334
work_keys_str_mv	AT yanaaisen suppressionofmultiplemyelomabymitochondrialtargeting AT mosheegatt suppressionofmultiplemyelomabymitochondrialtargeting AT rachelhertz suppressionofmultiplemyelomabymitochondrialtargeting AT eliasmeir suppressionofmultiplemyelomabymitochondrialtargeting AT jacobbartana suppressionofmultiplemyelomabymitochondrialtargeting
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Suppression of multiple myeloma by mitochondrial targeting

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