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Urolithin A and B Alter Cellular Metabolism and Induce Metabolites Associated with Apoptosis in Leukemic Cells.

ABSTRACT: Leukemia is persistently a significant cause of illness and mortality worldwide. Urolithins, metabolites of ellagic acid and ellagitannins produced by gut microbiota, showed better bioactive compounds liable for the health benefits exerted by ellagic acid and ellagitannins containing pomegranate and walnuts. Here, we assessed the potential antileukemic activities of both urolithin A and urolithin B. Results showed that both urolithin A and B significantly inhibited the proliferation of leukemic cell lines Jurkat and K562, among which urolithin A showed the more prominent antiproliferative capability. Further, urolithin treatment alters leukemic cell metabolism, as evidenced by increased metabolic rate and notable changes in glutamine metabolism, one-carbon metabolism, and lipid metabolism. Next, we evidenced that both urolithins equally promoted apoptosis in leukemic cell lines. Based on these observations, we concluded that both urolithin A and B alter leukemic cell metabolome, resulting in a halt of proliferation, followed by apoptosis. The data can be used for designing new combinational therapies to eradicate leukemic cells.

SUBMITTER: Alzahrani AM

PROVIDER: S-EPMC8196872 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Urolithin A and B Alter Cellular Metabolism and Induce Metabolites Associated with Apoptosis in Leukemic Cells.

Alzahrani Abdulaziz Musa AM Shait Mohammed Mohammed Razeeth MR Alghamdi Raed Ahmed RA Ahmad Abrar A Zamzami Mazin A MA Choudhry Hani H Khan Mohammad Imran MI

International journal of molecular sciences 20210522 11

Leukemia is persistently a significant cause of illness and mortality worldwide. Urolithins, metabolites of ellagic acid and ellagitannins produced by gut microbiota, showed better bioactive compounds liable for the health benefits exerted by ellagic acid and ellagitannins containing pomegranate and walnuts. Here, we assessed the potential antileukemic activities of both urolithin A and urolithin B. Results showed that both urolithin A and B significantly inhibited the proliferation of leukemic ...[more]

PMID: 34067305

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Project description:Multiple epidemics of chronic kidney disease of an unknown etiology (CKDu) have emerged in agricultural communities around the world. Many factors have been posited as potential contributors, but a primary cause has yet to be identified and the disease is considered likely multifactorial. Sugarcane workers are largely impacted by disease leading to the hypothesis that exposure to sugarcane ash produced during the burning and harvest of sugarcane could contribute to CKDu. Estimated exposure levels of particles under 10 μm (PM10) have been found to be exceptionally high during this process, exceeding 100 μg/m3 during sugarcane cutting and averaging ∼1800 μg/m3 during pre-harvest burns. Sugarcane stalks consist of ∼80% amorphous silica and generate nano-sized silica particles (∼200 nm) following burning. A human proximal convoluted tubule (PCT) cell line was subjected to treatments ranging in concentration from 0.025 μg/mL to 25 μg/mL of sugarcane ash, desilicated sugarcane ash, sugarcane ash-derived silica nanoparticles (SAD SiNPs) or manufactured pristine 200 nm silica nanoparticles. The combination of heat stress and sugarcane ash exposure on PCT cell responses was also assessed. Following 6-48 h of exposure, mitochondrial activity and viability were found to be significantly reduced when exposed to SAD SiNPs at concentrations 2.5 μg/mL or higher. Oxygen consumption rate (OCR) and pH changes suggested significant alteration to cellular metabolism across treatments as early as 6 h following exposure. SAD SiNPs were found to inhibit mitochondrial function, reduce ATP generation, increase reliance on glycolysis, and reduce glycolytic reserve. Metabolomic analysis revealed several cellular energetics pathways (e.g., fatty acid metabolism, glycolysis, and TCA cycle) are significantly altered across ash-based treatments. Heat stress did not influence these responses. Such changes indicate that exposure to sugarcane ash and its derivatives can promote mitochondrial dysfunction and disrupt metabolic activity of human PCT cells.

Dataset Information

Urolithin A and B Alter Cellular Metabolism and Induce Metabolites Associated with Apoptosis in Leukemic Cells.

Publications

Urolithin A and B Alter Cellular Metabolism and Induce Metabolites Associated with Apoptosis in Leukemic Cells.

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