Ribitol alters multiple metabolic pathways of central carbon metabolism with enhanced glycolysis: A metabolomics and transcriptomics profiling of breast cancer

• Published in: PloS one Vol. 17; no. 12; p. e0278711
• Main Authors: Tucker, Jason Driver, Doddapaneni, Ravi, Lu, Pei Juan, Lu, Qi Long
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.12.2022; Public Library of Science (PLoS)
• Subjects: Analysis; Antibodies; Biology and Life Sciences; Biomarkers; Biosynthesis; Breast cancer; Cancer therapies; Carbon; Cell growth; Diagnosis; Dystroglycan; Extracellular matrix; Fatty acids; Gene expression; Gene Expression Profiling; Genetic aspects; Gluconeogenesis; Glucose metabolism; Glutathione; Glycolysis; Hypotheses; Medical prognosis; Medicine and Health Sciences; Metabolic Networks and Pathways; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Metastasis; Mutation; Neoplasms; Nucleotides; Oxidative phosphorylation; Oxidative stress; Pentose; Phosphorylation; Physical Sciences; Ribitol; Ribose; Statistical analysis; Sugar; Transcriptomics; Tricarboxylic acid cycle; Xylitol; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0278711

Breast cancer is heterogenous in development and cell population with prognoses being highly dependent on numerous factors from driving mutations, biomarker expression and variation in extracellular environment, all affecting response to therapies. Recently, much attention has been given to the role of metabolic alteration in cancers, expanding from the Warburg effect to highlight unique patterns in different cancer cell populations for improving diagnostic and therapeutic approaches. We recently reported on modulation of mannosylation of α-dystroglycan with the metabolite ribitol in breast cancer lines. Here we investigate the effects of pentose sugars ribitol, ribose, and xylitol media supplementation in breast cancer cells by metabolomics and differential gene expression profiling. This combined approach revealed distinctive patterns of alterations in metabolic pathways by ribitol, contrasted with the closely related pentose ribose and pentitol xylitol. Significantly, ribitol supplementation enhances utilization of glucose by glycolysis, whereas ribose improves oxidative phosphorylation and fatty acid synthesis. Ribitol supplementation also increased levels of reduced glutathione (associated with a decrease in oxidative phosphorylation, gluconeogenesis), where ribose supplementation elevated levels of oxidized glutathione (GSSG) indicating an increase in oxidative stress. Treatment with ribitol also enhanced nucleotide biosynthesis. The apparent TCA cycle dysregulation, with distinctive pattern in response to the individual pentitol and pentose, such as ribitol increasing succinate and fumarate while decreasing citrate, demonstrate the adaptive capability of cancer cells to nutritional environment. This metabolic reprogramming presents new avenues for developing targeted therapies to cancers with metabolites, especially in combination with other drug treatments.