Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer

Abstract Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the se...

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Autores principales:	Paavo Raittinen, Kati Niemistö, Erika Pennanen, Heimo Syvälä, Seppo Auriola, Jarno Riikonen, Terho Lehtimäki, Pauliina Ilmonen, Teemu Murtola
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/25b99540e9c54e4abc8a9297592afb94
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spelling	oai:doaj.org-article:25b99540e9c54e4abc8a9297592afb942021-12-02T16:26:21ZCirculatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer10.1038/s41598-020-68868-52045-2322https://doaj.org/article/25b99540e9c54e4abc8a9297592afb942020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68868-5https://doaj.org/toc/2045-2322Abstract Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the serum. Statin effect on serum or intraprostatic lipidome profiles in prostate cancer patients has not been explored. We studied changes in the serum metabolomic and prostatic tissue lipidome after high-dose 80 mg atorvastatin intervention to expose biological mechanisms causing the observed survival benefit. Our randomized, double-blind, placebo-controlled clinical trial consisted of 103 Finnish men with prostate cancer. We observed clear difference in post-intervention serum lipoprotein lipid profiles between the study arms (median classification error 11.7%). The atorvastatin effect on intraprostatic lipid profile was not as clear (median classification error 44.7%), although slightly differing lipid profiles by treatment arm was observed, which became more pronounced in men who used atorvastatin above the median of 27 days (statin group median classification error 27.2%). Atorvastatin lowers lipids important for adaptation for hypoxic microenvironment in the prostate suggesting that prostate cancer cell survival benefit associated with statin use might be mediated by both, local and systemic, lipidomic/metabolomic profile changes.Paavo RaittinenKati NiemistöErika PennanenHeimo SyväläSeppo AuriolaJarno RiikonenTerho LehtimäkiPauliina IlmonenTeemu MurtolaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paavo Raittinen Kati Niemistö Erika Pennanen Heimo Syvälä Seppo Auriola Jarno Riikonen Terho Lehtimäki Pauliina Ilmonen Teemu Murtola Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer
description	Abstract Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the serum. Statin effect on serum or intraprostatic lipidome profiles in prostate cancer patients has not been explored. We studied changes in the serum metabolomic and prostatic tissue lipidome after high-dose 80 mg atorvastatin intervention to expose biological mechanisms causing the observed survival benefit. Our randomized, double-blind, placebo-controlled clinical trial consisted of 103 Finnish men with prostate cancer. We observed clear difference in post-intervention serum lipoprotein lipid profiles between the study arms (median classification error 11.7%). The atorvastatin effect on intraprostatic lipid profile was not as clear (median classification error 44.7%), although slightly differing lipid profiles by treatment arm was observed, which became more pronounced in men who used atorvastatin above the median of 27 days (statin group median classification error 27.2%). Atorvastatin lowers lipids important for adaptation for hypoxic microenvironment in the prostate suggesting that prostate cancer cell survival benefit associated with statin use might be mediated by both, local and systemic, lipidomic/metabolomic profile changes.
format	article
author	Paavo Raittinen Kati Niemistö Erika Pennanen Heimo Syvälä Seppo Auriola Jarno Riikonen Terho Lehtimäki Pauliina Ilmonen Teemu Murtola
author_facet	Paavo Raittinen Kati Niemistö Erika Pennanen Heimo Syvälä Seppo Auriola Jarno Riikonen Terho Lehtimäki Pauliina Ilmonen Teemu Murtola
author_sort	Paavo Raittinen
title	Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer
title_short	Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer
title_full	Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer
title_fullStr	Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer
title_full_unstemmed	Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer
title_sort	circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/25b99540e9c54e4abc8a9297592afb94
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Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer

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