25-Hydroxycholesterol Induces Death Receptor-mediated Extrinsic and Mitochondria-dependent Intrinsic Apoptosis in Head and Neck Squamous Cell Carcinoma Cells.

Abstract:

BACKGROUND/AIM:Oxysterol plays important physiological roles in diverse biological processes including apoptosis. However, the mechanisms underlying oxysterol-induced apoptosis remain unknown. 25-hydroxycholesterol (25-HC) is an oxysterol synthesized by cholesterol 25-hydroxylase from cholesterol during sterol metabolism. The aim of present study was to investigate 25-HC-induced apoptosis and associated signalling pathways in FaDu cells, which is originated form human head and neck squamous cell carcinoma cells. MATERIALS AND METHODS:25-HC-induced apoptosis was investigated by cell cytotoxicity assay using MTT, cell viability assay using cell LIVE/DEAD cell viability assay, haematoxylin & eosin staining, nuclear staining, fluorescence-activated cell sorting, western blotting using specific antibodies associated with extrinsic and intrinsic apoptosis pathways, and caspase-3/-7 activity assay in FaDu cells. RESULTS:25-HC dose-dependently decreased the viability of FaDu cells and up-regulated apoptotic events, such as alteration in morphology, and nuclear condensation. Flow cytometric analysis showed an increase in apoptotic population upon 25-HC treatment, suggesting that 25-HC induces apoptosis in FaDu cells. Moreover, 25-HC-induced apoptosis in FaDu cells was dependent on the activation of caspases by Fas antigen ligand-triggered death receptor-mediated extrinsic pathway and mitochondria-dependent intrinsic pathway via mitogen activated protein kinases. CONCLUSION:Cholesterol-derived oxysterol, 25-HC has potential anti-cancer function in FaDu cells and may have potential properties for the discovery of anti-cancer agents.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

You JS,Lim H,Kim TH,Oh JS,Lee GJ,Seo YS,Kim DK,Yu SK,Kim HJ,Kim CS,Kim JS

doi

10.21873/anticanres.14009

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

779-788

issue

2

eissn

0250-7005

issn

1791-7530

pii

40/2/779

journal_volume

40

pub_type

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