Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Downregulation of dihydrolipoyl dehydrogenase by UVA suppresses melanoma progression via triggering oxidative stress and altering energy metabolism

Authors
Yumnam, SilviaKang, Min CheolOh, Seung HyunKwon, Hak CheolKim, Jin ChulJung, Eun SungLee, Choong HwanLee, Ai-YoungHwang, Jong-IkKim, Sun Yeou
Issue Date
1월-2021
Publisher
ELSEVIER SCIENCE INC
Keywords
A375; Autophagy; Dihydrolipoyl dehydrogenase; MNT1; Melanoma; NAD(+)/NADH; ROS; UVA
Citation
FREE RADICAL BIOLOGY AND MEDICINE, v.162, pp.77 - 87
Indexed
SCIE
SCOPUS
Journal Title
FREE RADICAL BIOLOGY AND MEDICINE
Volume
162
Start Page
77
End Page
87
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/137828
DOI
10.1016/j.freeradbiomed.2020.11.037
ISSN
0891-5849
Abstract
Melanoma, the most severe form of skin cancer, has poor prognosis and is resistant to chemotherapy. Targeting cancer metabolism is a promising approach in cancer therapeutics. Dihydrolipoyl dehydrogenase (DLD) is a mitochondrial enzyme with diaphorase activity. Here we report a pivotal role of DLD in melanoma cell progression and proliferation. Suppression DLD expression by low intensity UVA (125 mJ/cm(2) ) increased intracellular ROS production and decreased mitochondrial membrane potential thereby inducing autophagy cell death which were confirmed by increased LC3BII and decreased p62 expression in melanoma cells. Knockdown of DLD in melanoma cells also showed similar results. More so, suppression of DLD significantly inhibits in vivo melanoma growth and tumor proliferation. In addition, suppression of DLD increased the NAD+/NADH ratio in melanoma cells and also inhibits TCA cycle related metabolites. DLD downregulation markedly increased alpha-ketoglutarate and decreased succinic acid suggesting that DLD suppression may have decreased TCA cycle downstream metabolites, resulting in the alteration of mitochondrial energy metabolism Thus the downregulation of DLD induced autophagic cell death in melanoma cells and inhibits in vivo tumor growth and proliferation by increasing ROS production and altering energy metabolism. Our findings suggest that DLD plays a pivotal role in melanoma progression and proliferation.
Files in This Item
There are no files associated with this item.
Appears in
Collections
Graduate School > Department of Biomedical Sciences > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Hwang, Jong Ik photo

Hwang, Jong Ik
의과학과
Read more

Altmetrics

Total Views & Downloads

BROWSE