5-lipoxygenase mediates docosahexaenoyl ethanolamide andN-arachidonoyl-L-alanine-induced reactive oxygen species production andinhibition of proliferation of head and neck squamous cell carcinomacells

Collection with item attached
2016
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473448.do
DOI
10.1186/s12885-016-2499-3
Title
5-lipoxygenase mediates docosahexaenoyl ethanolamide andN-arachidonoyl-L-alanine-induced reactive oxygen species production andinhibition of proliferation of head and neck squamous cell carcinomacells
Description
This research was supported by Basic Science Research Program throughthe National Research Foundation of Korea (NRF) funded by the Ministryof Education, Science and Technology (NRF-2012R1A1A2003968) and grant no03-2011-0140 from the SNUH Research Fund.
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.
provenance
Made available in Cube on 2018-09-28T10:19:51Z (GMT). No. of bitstreams: 0
language
English
author
Park, Seok-Woo
Hah, J. Hun
Oh, Sang-Mi
Jeong, Woo-Jin
Sung, Myung-Whun
orcid
Hah, J. Hun/0000-0002-5110-012X
accessioned
2018-09-28T10:19:51Z
available
2018-09-28T10:19:51Z
issued
2016
citation
BMC CANCER(16)
issn
1471-2407
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473448.do
Funder
교육부
Funding Program
일반연구자지원
Project ID
1345226511
Jurisdiction
Rep.of Korea
Project Name
Investigation on the role of COX-2 expression in cancer-specific killing action of anti-cancer drugs
rights
openAccess
subject
Endocannabinoid
DHEA
NALA
5-lipoxygenase
ROS
Head and neck cancer
type
article


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