Co-treatment with melatonin and ortho-topolin riboside reduces cell viability by altering metabolic profiles in non-small cell lung cancer cells.

Lung cancer is a highly prevalent and lethal malignancy worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of cancer-related deaths. In this study, the effects of co-treatment with melatonin and ortho-topolin riboside (oTR) on the cell viability and alteration of metabolites and transcripts were investigated in NSCLC cells using gas chromatography-mass spectrometry (GC-MS) and next-generation sequencing (NGS). The co-treatment of melatonin and oTR exhibited synergistic effects on the reduction of cell viability and alteration of metabolic and transcriptomic profiles in NSCLC cells. We observed that the co-treatment inhibited glycolytic function and mitochondria respiration, and downregulated glycine, serine and threonine metabolism alongside tyrosine metabolism in NSCLC cells. In the glycine, serine and threonine metabolism pathway, the co-treatment resulted in a significant 8.4-fold reduction in the expression level of the SDS gene, which encodes the enzyme responsible for the breakdown of serine to pyruvate. Moreover, co-treatment decreased the gene expression of TH, DDC, and CYP1A1 in tyrosine metabolism. Additionally, we observed that the co-treatment resulted in a significant 146.9-fold reduction in the expression of the DISC1 gene. The alteration in metabolites and transcript expressions might provide information to explain the cytotoxicity of co-treatment of melatonin and oTR in NSCLC cells. Our study presents insights into the synergistic anticancer effect of the co-treatment of melatonin and oTR, which could be a potential future therapeutic strategy for the treatment of NSCLC patients.

Melosira nummuloides Ethanol Extract Ameliorates Alcohol-Induced Liver Injury by Affecting Metabolic Pathways.

Melosira nummuloides is a microalga with a nutritionally favorable polyunsaturated fatty acid profile. In the present study, M. nummuloides ethanol extract (MNE) was administered to chronic-binge alcohol-fed mice and alcohol-treated HepG2 cells, and its hepatoprotective effects and underlying mechanisms were investigated. MNE administration reduced triglyceride (TG), total cholesterol (T-CHO), and liver injury markers, including aspartate transaminase (AST) and alanine transaminase (ALT), in the serum of chronic-binge alcohol-fed mice. However, MNE administration increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK/AMPK) and PPARα, which was accompanied by a decrease in SREBP-1; this indicates that MNE can inhibit adipogenesis and improve fatty acid oxidation. Moreover, MNE administration upregulated the expression of antioxidant enzymes, including SOD, NAD(P)H quinone dehydrogenase 1, and GPX, and ameliorated alcohol-induced inflammation by repressing the Akt/NFκB/COX-2 pathway. Metabolomic analysis revealed that MNE treatment modulated many lipid metabolites in alcohol-treated HepG2 cells. Our study findings provide evidence for the efficacy and mechanisms of MNE in ameliorating alcohol-induced liver injury.

Melatonin Treatment Enhances the Growth and Productivity of Useful Metabolites in the In Vitro Culture of Spirodela polyrhiza.

Spirodela polyrhiza (Araceae family) is a duckweed species that serves as a potential resource for feed, food, bioremediation, and pharmaceutical applications. In this study, we assessed the effects of different concentrations of melatonin (0, 0.1, 1, and 10 µM) on the growth of S. polyrhiza during in vitro culture and the metabolic profiles and productivities of useful metabolites using gas chromatography-mass spectrometry coupled with multivariable statistical analysis. We found that exogenous melatonin significantly improved the total dry weight and altered the metabolic profiles of S. polyrhiza cultures. Melatonin significantly enhanced the cellular production of useful metabolites, such as γ-aminobutyric acid, dopamine, threonine, valine, and phytosterols. The volumetric productivities (mg/L) of γ-aminobutyric acid, dopamine, campesterol, ß-sitosterol, and stigmasterol were the highest in the presence of 10 µM melatonin on day 12. Moreover, the productivities of ascorbic acid and serotonin were the highest in the presence of 1 µM melatonin on day 12. Therefore, melatonin could be used to enhance the production of biomass and useful metabolites during large-scale S. polyrhiza cultivation in cosmetic, food/feed, and pharmaceutical industries.