Group items tagged

chemosensitizing

pharmacological concentrations of AA can sensitize cancer cells to chemotherapy, enhancing its antineoplastic effect

synergistic effect with conventional chemotherapeutic drugs is a fact already reported, in various types of cancer, by numerous authors, namely in pancreatic (Espey et al., 2011), prostate (Gilloteaux et al., 2014), lung (Lee et al., 2017), breast (Kurbacher et al., 1996; Wu et al., 2017) and ovarian (Ma et al., 2014) cancers.

chemosensitizing effect of vitamin C has already been proven by several authors in various types of cancer

intravenous pharmacological concentrations, may not only potentiate the effects of conventional chemotherapy, but also improve the quality of life of cancer patients

AA reinforced the anti-proliferative activity of 5-FU

Combined treatment induced a reduction of 11.5% and 43% in cell viability compared with AA or Iri therapies, respectively, emphasizing the synergistic effect

cytotoxic effect occurred with treatment with Iri alone, but also this effect was further potentiated by the presence of AA.

association of AA with Oxa showed very promising results, considering that a synergistic effect was demonstrated, in almost all conditions

AA and Oxa seem to act synergistically by the activation of the intrinsic pathway of apoptosis, translated on the statistically significant increase of the ratio between BAX and BCL-2 proteins, which in turn is associated with a decrease of Δψm

Previous results obtained by our group showed that AA mediates reactive oxygen species (ROS) formation capable of irreparably damaging DNA

oxidative role of AA may be a key factor on the synergistic anti-cancer mechanism

it is hydrolyzed to glutamate and ammonia by glutaminase (‘glutaminolysis’)

Glutamate, produced from glutamine by glutaminase and glutamine amidotransferase activities, may be further metabolized to alpha ketoglutarate and provide a carbon skeleton source for the mitochondrial tricarboxylic acid cycle (TCA cycle)

Glutamine-derived glutamate is also involved in the synthesis of the reducing equivalent glutathione, vital to maintaining cellular redox status

Many tumors become largely dependent on glutamine to provide carbon and nitrogen building blocks needed for proliferation

In cancer model systems, Eagle and colleagues first demonstrated tumor cells in culture require supplementation with exogenous glutamine for efficient proliferation

It was subsequently shown that when deprived of glutamine tumor cells undergo apoptosis

The most well-characterized oncogene to regulate glutamine metabolism is MYC (9), which enhances glutaminase expression, upregulates glutamine transporters, and enhances glutamine utilization in energy production and biosynthesis

Other pro-tumorigenic regulators such as KRAS and mTOR, as well as tumor suppressors (p53, VHL) have also been associated with alterations in glutamine metabolism

Tumor cells are highly adaptable and alter nutrient uptake and metabolic networks to resist single agent glutaminase inhibition

cells in the microenvironment of several tumor types upregulate glutamine production, thereby enabling tumor cells to escape glutaminase inhibition