27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumor DOI Open Access

Silia Ayadi,

Silvia Friedrichs,

Régis Soulès

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 10, 2023

ABSTRACT Oncosterone (6-oxo-cholestane-3β,5α-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha positive breast cancer (ER(+) BC) triple negative cancers (TN BC). OCDO oxysterol formed in three steps from cholesterol: 1) oxygen addition at the double bond to give α- or β-isomers of 5,6-epoxycholestanols (5,6-EC), 2) hydrolyses epoxide ring 5,6-ECs cholestane-3β,5α,6β-triol (CT), 3) oxidation C6 hydroxyl CT OCDO. On other hand, cholesterol can be hydroxylated by CYP27A1 ultimate methyl carbon its side chain 27-hydroxycholesterol (27HC), which for ER(+) BC. It currently unknown whether precursors position C27 CYP27A1, as impact such modification proliferation TN BC cells. We investigated, herein, 27-hydroxylated-5,6-ECs, -CT -OCDO exist metabolites produced cells expressing CYP27A1. report, first time, that these compounds human. pharmacological genetic evidences responsible their production. Importantly, we found 27-hydroxy-OCDO (27H-OCDO) inhibits blocks 27-HC induced cells, showing this metabolic conversion commutes proliferative properties into antiproliferative ones. These data suggest unprecedented role control carcinogenesis inhibiting activities oncosterone 27-HC.

Язык: Английский

27-Hydroxylation of oncosterone by CYP27A1 switches its activity from pro-tumor to anti-tumor DOI Creative Commons

Silia Ayadi,

Silvia Friedrichs,

Régis Soulès

и другие.

Journal of Lipid Research, Год журнала: 2023, Номер 64(12), С. 100479 - 100479

Опубликована: Ноя. 20, 2023

Oncosterone (6-oxo-cholestane-3β,5α-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha-positive breast cancer (ER(+) BC) triple-negative cancers (TN BC). OCDO oxysterol formed in three steps from cholesterol: 1) oxygen addition at the double bond to give α- or β- isomers of 5,6-epoxycholestanols (5,6-EC), 2) hydrolyses epoxide ring 5,6-ECs cholestane-3β,5α,6β-triol (CT), 3) oxidation C6 hydroxyl CT OCDO. On other hand, cholesterol can be hydroxylated by CYP27A1 ultimate methyl carbon its side chain 27-hydroxycholesterol ((25R)-Cholest-5-ene-3beta,26-diol, 27HC), which for ER(+) BC. It currently unknown whether precursors position C27 CYP27A1, as impact such modification proliferation TN BC cells. We investigated, herein, 27H-5,6-ECs ((25R)-5,6-epoxycholestan-3β,26-diol), 27H-CT ((25R)-cholestane-3β,5α,6β,26-tetrol) 27H-OCDO ((25R)-cholestane-6-oxo-3β,5α,26-triol) exist metabolites produced cells expressing CYP27A1. report, first time, that these compounds humans. pharmacological genetic evidence responsible their production. Importantly, we found 27-hydroxy-OCDO (27H-OCDO) inhibits cell blocks 27-HC-induced cells, showing this metabolic conversion commutes proliferative properties into antiproliferative ones. These data suggest unprecedented role control carcinogenesis inhibiting activities oncosterone 27-HC.

Язык: Английский

Процитировано

5
Editorial: Lipids, lipid oxidation, and cancer: from biology to therapeutics DOI Creative Commons
Sérgio Paulo Bydlowski, Marc Poirot

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Апрель 19, 2024

Keywords: lipids, lipid oxidation, lipoprotein, cancer, immune cells, fatty acid, triple-negative breast HPV

Язык: Английский

Процитировано

0
27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumor DOI Open Access

Silia Ayadi,

Silvia Friedrichs,

Régis Soulès

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 10, 2023

ABSTRACT Oncosterone (6-oxo-cholestane-3β,5α-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha positive breast cancer (ER(+) BC) triple negative cancers (TN BC). OCDO oxysterol formed in three steps from cholesterol: 1) oxygen addition at the double bond to give α- or β-isomers of 5,6-epoxycholestanols (5,6-EC), 2) hydrolyses epoxide ring 5,6-ECs cholestane-3β,5α,6β-triol (CT), 3) oxidation C6 hydroxyl CT OCDO. On other hand, cholesterol can be hydroxylated by CYP27A1 ultimate methyl carbon its side chain 27-hydroxycholesterol (27HC), which for ER(+) BC. It currently unknown whether precursors position C27 CYP27A1, as impact such modification proliferation TN BC cells. We investigated, herein, 27-hydroxylated-5,6-ECs, -CT -OCDO exist metabolites produced cells expressing CYP27A1. report, first time, that these compounds human. pharmacological genetic evidences responsible their production. Importantly, we found 27-hydroxy-OCDO (27H-OCDO) inhibits blocks 27-HC induced cells, showing this metabolic conversion commutes proliferative properties into antiproliferative ones. These data suggest unprecedented role control carcinogenesis inhibiting activities oncosterone 27-HC.

Язык: Английский

Процитировано

0