BMB Reports Papers in Press available online.

Search Papers In Press
This galley proof is being listed electronically before publishing the final manuscript (It's not final version).

Melatonin inhibits glycolysis in hepatocellular carcinoma cells by downregulating mitochondrial respiration and mTORC1 activity
Seunghyeong Lee1,2,# (Post PhD), Jun-Kyu Byun3,4,# (Research Professor), Na-Young Kim4 (Clinical professor), Jonghwa Jin 4 (clinical instructor), Hyein Woo4 (clinical instructor), Yeon-Kyung Choi 3,5,* (Assistant professor), Keun-Gyu Park 1,3,4 (Professor)
1Department of Biomedical Science, Kyungpook National University,
2BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University,
3Research Institute of Aging and Metabolism, Kyungpook National University,
4Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital,
5Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital
Multiple mechanisms have been suggested to explain the chemopreventive and tumor-inhibitory effects of melatonin. Despite growing evidence supporting melatonin-induced mitochondrial dysfunction, it remains largely unknown how this phenomenon modulates metabolic reprogramming in cancer cells. The aim of this study was to identify the mechanism underlying the anti-proliferative and apoptotic effects of melatonin, which is known to inhibit glycolysis. We analyzed the time-dependent effects of melatonin on mitochondrial respiration and glycolysis in liver cancer cells and found that from a cell bioenergetic point of view, melatonin caused an acute reduction in mitochondrial respiration, but increased reactive oxygen species production, thereby inhibiting mTORC1 activity from an early stage post-treatment without affecting glycolysis. However, administration of melatonin for a longer time reduced expression of c-Myc protein, thereby suppressing glycolysis via downregulation of HK2 and LDHA. The data presented herein suggest that melatonin suppresses mitochondrial respiration and glycolysis simultaneously in HCC cells, leading to anti-cancer effects. Thus, melatonin has potential as an adjuvant agent for therapy of liver cancer.
Abstract, Accepted Manuscript(in press) [Submitted on December 9, 2021, Accepted on March 23, 2022]
  Copyright © KSBMB. All rights reserved. / Powered by INFOrang Co., Ltd