Inhibition of glycolysis disrupts cellular antioxidant defense and sensitizes HepG2 cells to doxorubicin treatment.

08:00 EDT 30th March 2019 | BioPortfolio

Summary of "Inhibition of glycolysis disrupts cellular antioxidant defense and sensitizes HepG2 cells to doxorubicin treatment."

Increased glucose consumption is a known hallmark of cancer cells. Increased glycolysis provides ATP, reducing agents and substrates for macromolecular synthesis in intensely dividing cells. Therefore, inhibition of glycolysis is one strategy in anticancer therapy as well as in improved efficacy of conventional anticancer chemotherapeutic agents. One such agent is doxorubicin (DOX), but the mechanism of sensitization of tumor cells to DOX by inhibition of glycolysis has not been fully elucidated. As oxidative stress is an important phenomenon accompanying DOX action and antioxidant defense is closely related to energy metabolism, the aim of the study was the evaluation of oxidative stress markers and antioxidant abilities of cancer cells treated with DOX while glycolysis is inhibited. HepG2 cells were treated with DOX and one of three glycolysis inhibitors: 2-deoxyglucose, dichloroacetate or 3-promopyruvate. To evaluate the possible interaction mechanisms, we assessed mRNA expression of selected genes related to energy metabolism and antioxidant defense; oxidative stress markers; and reduced glutathione (GSH) and NADPH levels. Additionally, glutamine consumption was measured. It was demonstrated that the chemotherapeutic agent and glycolysis inhibitors induced oxidative stress and associated damage in HepG2 cells. However, simultaneous treatment with both agents resulted in even greater lipid peroxidation and a significant reduction in GSH and NADPH levels. Moreover, in the presence of the drug and an inhibitor, HepG2 cells had a reduced ability to take up glutamine. These results indicated that cells treated with DOX while glycolysis was inhibited had significantly reduced ability to produce NADPH and antioxidant defenses.


Journal Details

This article was published in the following journal.

Name: FEBS open bio
ISSN: 2211-5463


DeepDyve research library

PubMed Articles [12730 Associated PubMed Articles listed on BioPortfolio]

Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism.

Acetaminophen (APAP) is one of the most commonly used analgesics worldwide, and overdoses are associated with lactic acidosis, hepatocyte toxicity, and acute liver failure due to oxidative stress and ...

Flavonoids, phenolic acids, carotenoids and antioxidant activity of fresh eating citrus fruits, using the coupled in vitro digestion and human intestinal HepG2 cells model.

With in-vitro digestion and human intestinal HepG2 cells, we analyzed the bioaccessibility and cell uptake of phytochemicals and determined the cellular antioxidant capacity (CAA) of fresh eating citr...

Toxicity of diuron in HepG2 cells and zebrafish embryos.

Diuron is an herbicide, which is used to control a wide variety of annual and perennial broadleaf, grassy weeds, and mosses. However, the toxicity of diuron in HepG2 cells and zebrafish embryos was un...

A Potent and Selective ULK1 Inhibitor Suppresses Autophagy and Sensitizes Cancer Cells to Nutrient Stress.

In response to stress, cancer cells generate nutrients and energy through a cellular recycling process called autophagy, which can promote survival and tumor progression. Accordingly, autophagy inhibi...

Microcystin-LR regulates circadian clock and antioxidant gene expression in cultured rat cardiomyocytes.

Microcystins are waterborne environmental toxins that induce oxidative stress and cause injuries in the heart. On the other hand, many physiological processes, including antioxidant defense, are under...

Clinical Trials [2353 Associated Clinical Trials listed on BioPortfolio]

Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes

Oxidative stress has been implicated in the development and complications of diabetes. Hyperglycemia and insulin resistance or insufficiency in diabetes can cause oxidative stress by exces...

The Occurence of Inflammation and Oxidative Stress in Lung Diseases

Reactive oxygen species (ROS) are suggested to play a pivotal role in ILD. Little is known, however, about the endogenous antioxidant levels in ILD that can offer protection against ROS. I...

The Effect of Quercetin in Sarcoidosis

The exact cause of the chronic lung disease sarcoidosis is still unknown. Consequently, a complete efficacious treatment is still not available. Earlier studies indicate an important key r...

To Investigate Primary Irritation Potential of Four Skin Serum Products on Human Subjects Assessed by 24 Hour Patch Test

To assess the irritation potential of four prototype daily defense serum formulations after 24 (± 2) hours under semi-occlusive patch application to the skin of healthy volunteers.

Cross-over Double-blind Intervention to Investigate the Effects of Defined Antioxidant-containing Drinks on Time Course of Antioxidant Capacity

The aim of this project is to measure the differences in antioxidant capacity at different time points after consuming a single dose of antioxidant-containing drink (vitamin C or epicatech...

Medical and Biotech [MESH] Definitions

A fungal metabolite that blocks cytoplasmic cleavage by blocking formation of contractile microfilament structures resulting in multinucleated cell formation, reversible inhibition of cell movement, and the induction of cellular extrusion. Additional reported effects include the inhibition of actin polymerization, DNA synthesis, sperm motility, glucose transport, thyroid secretion, and growth hormone release.

Organs involved in the production of BLOOD, including the cellular and the molecular components essential in providing defense against foreign organisms or substances.

A nitroimidazole that sensitizes hypoxic tumor cells that are normally resistant to radiation therapy.

Nucleotide sequences that are found in the PROMOTER REGIONS of the genes of stress-responsive and cytoprotective proteins, such as those encoding antioxidant and PHASE II DETOXIFICATION enzymes. NF-E2-RELATED FACTOR 2 containing transcription factors bind to these elements during induction of these genes.

A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.

Quick Search


DeepDyve research library

Relevant Topics

Cancer Disease
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...

Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...

Mental Health
Adhd Anorexia Depression Dyslexia Mental Health Psychiatry Schizophrenia Stress Mental health, although not being as obvious as physical health, is very important, causing great unhappiness to those affected, causing add...

Searches Linking to this Article