Home
Resources
Publications
5-lipoxygenase Mediates Docosahexaenoyl Ethanolamide and N-arachidonoyl-L-alanine-induced Reactive Oxygen Species Production and Inhibition of Proliferation of Head and Neck Squamous Cell Carcinoma Cells

5-lipoxygenase Mediates Docosahexaenoyl Ethanolamide and N-arachidonoyl-L-alanine-induced Reactive Oxygen Species Production and Inhibition of Proliferation of Head and Neck Squamous Cell Carcinoma Cells

Seok-Woo Park, J Hun Hah, Sang-Mi Oh, Woo-Jin Jeong, Myung-Whun Sung

BMC Cancer. 2016 Jul 13;16:458.

PMID: 27411387

Abstract:

Background:
Endocannabinoids have recently drawn attention as promising anti-cancer agents. We previously observed that anandamide (AEA), one of the representative endocannabinoids, effectively inhibited the proliferation of head and neck squamous cell carcinoma (HNSCC) cell lines in a receptor-independent manner. In this study, using HNSCC cell lines, we examined the anti-cancer effects and the mechanisms of action of docosahexaenoyl ethanolamide (DHEA) and N-arachidonoyl-L-alanine (NALA), which are polyunsaturated fatty acid (PUFA)-based ethanolamides like AEA.
Methods and results:
DHEA and NALA were found to effectively inhibit HNSCC cell proliferation. These anti-proliferative effects seemed to be mediated in a cannabinoid receptor-independent manner, since the antagonist of cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (VR1), two endocannabinoid receptors, did not reverse the ability of DHEA and NALA to induce cell death. Instead, we observed an increase in reactive oxygen species (ROS) production and a decrease of phosphorylated Akt as a result of DHEA and NALA treatment. Antioxidants efficiently reversed the inhibition of cell proliferation and the decrease of phosphorylated Akt induced by DHEA and NALA; inhibition of 5-lipoxygenase (5-LO), which is expected to be involved in DHEA- and NALA-degradation pathway, also partially blocked the ability of DHEA and NALA to inhibit cell proliferation and phosphorylated Akt. Interestingly, ROS production as a result of DHEA and NALA treatment was decreased by inhibition of 5-LO.
Conclusions:
From these findings, we suggest that ROS production induced by the 5-LO pathway mediates the anti-cancer effects of DHEA and NALA on HNSCC cells. Finally, our findings suggest the possibility of a new cancer-specific therapeutic strategy, which utilizes 5-LO activity rather than inhibiting it.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP162758943	Docosahexaenoyl ethanolamide		162758-94-3	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: