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.

• Authors: Jae-Seek You, Hyangi Lim, Tae-Hyeon Kim, Ji-Su Oh, Gyeong-Je Lee, Yo-Seob Seo, DO Kyung Kim, Sun-Kyoung Yu, Heung-Joong Kim, Chun Sung Kim, Jae-Sung Kim
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 2 Pg. 779-788 (Feb 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 32014920 (Publication Type: Journal Article)
• Copyright: Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Hydroxycholesterols
• 25-hydroxycholesterol

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Humans
• Hydroxycholesterols (pharmacology, therapeutic use)
• Squamous Cell Carcinoma of Head and Neck (drug therapy, pathology)