Melatonin suppresses Akt/mTOR/S6K activity, induces cell apoptosis, and synergistically inhibits cell growth with sunitinib in renal carcinoma cells via reversing Warburg effect.

ABSTRACT:

Background

Metabolic alteration drives renal cell carcinoma (RCC) development, while the impact of melatonin (MLT), a neurohormone secreted during darkness, on RCC cell growth and underlying mechanisms remains unclear.

Methods

We detected concentration of metabolites through metabolomic analyses using UPLC-MS/MS, and the oxygen consumption rate was determined using the Seahorse Extracellular Flux analyzer.

Results

We observed that MLT effectively inhibited RCC cell growth both in vitro and in vivo. Additionally, MLT increased ROS levels, suppressed antioxidant enzyme activity, and induced apoptosis. Furthermore, MLT treatment upregulated key TCA cycle metabolites while reducing aerobic glycolysis products, leading to higher oxygen consumption rate, ATP production, and

SUBMITTER: Xue KH 

PROVIDER: S-EPMC10472857 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature