Molecular docking and dynamic studies of a potential therapeutic target inhibiting glyoxalase system: Metabolic action of the 3, 3 '- [3- (5-chloro-2-hydroxyphenyl) -3-oxopropane-1, 1-diyl] - Bis-4-hydroxycoumarin leads overexpression of the intracellular level of methylglyoxal and induction of a pro-apoptotic phenomenon in a hepatocellular carcinoma model
TL;DR: In this article, the authors demonstrate the inhibitory effect of 3, 3'-[3-(5-chloro-2-hydroxyphenyl)-3-oxopropane-1, 1-diyl] Bis (4-hydroxycoumarin) on the glyoxalase system, and indirectly its anticancer activity.
About: This article is published in Chemico-Biological Interactions.The article was published on 2021-05-11. It has received 2 citations till now. The article focuses on the topics: Glyoxalase system & Methylglyoxal.
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TL;DR: In this article , the authors evaluated the effect of pharmacological antidiabetic dose of metformin (used in cancer studies) at the early stages of HCC versus the sub-pharmacological dose.
Abstract: Hepatocellular carcinoma (HCC) is the fourth cause of cancer mortality worldwide. Metformin is an antidiabetic drug that showed a prophylactic effect in the early stages of some cancers. This study aimed to reevaluate the anticarcinogenic effect of metformin in a cancer model not associated with diabetes. Also, to evaluate the effect of pharmacological antidiabetic dose of metformin (used in cancer studies) at the early stages of HCC versus the sub-pharmacological dose. HCC was induced by a single i.p injection of diethylnitrosamine followed by 16 biweekly i.p injections of carbon-tetrachloride. Metformin was i.p injected (25 or 250 mg/kg) post HCC induction for four weeks. The low dose of metformin suppressed HCC by reducing liver biomarkers levels, and the number and size of hepatic nodules. Also, metformin (25 mg/kg) downstaged HCC via activating Bax and suppressing Bcl-2, VEGF, and PCNA. Mice treated with metformin (250 mg/kg) exhibited lactic acidosis, death, and insignificant differences in nodules’ number and size and immunohistochemical markers compared to the HCC group. This study concluded that the pharmacological dose of metformin cannot be used at advanced stages of HCC, while the sub-pharmacological dose of metformin showed a promising anticarcinogenic effect in chemically-induced HCC model not associated with diabetes. .
TL;DR: Wang et al. as discussed by the authors developed a multi-strategy targeting liposomes that can improve the targeting ability and specifically recognize tumor cells and tumor-like stem cells, which is a promising system for the treatment of HCC.
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TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Abstract: In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed “the Warburg effect.” Aerobic glycolysis is an inefficient way to generate adenosine 5′-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
12,380 citations
TL;DR: The Warburg effect of aerobic glycolysis is re-examine and a framework for understanding its contribution to the altered metabolism of cancer cells is established.
2,081 citations
TL;DR: Recent results confirm the prominent role of astrocytes in glutathione metabolism and the defense against reactive oxygen species in brain and suggest an involvement of a compromised astroglial glutATHione system in the oxidative stress reported for neurological disorders.
1,582 citations
TL;DR: Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.
937 citations
TL;DR: The objective of this review is to present the most recent research on the cancer-specific role of glycolysis including their non-glycolytic functions in order to explore the potential for therapeutic opportunities.
Abstract: Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the “hallmarks of cancer”. This metabolic phenotype is characterized by preferential dependence on glycolysis (the process of conversion of glucose into pyruvate followed by lactate production) for energy production in an oxygen-independent manner. Although glycolysis is less efficient than oxidative phosphorylation in the net yield of adenosine triphosphate (ATP), cancer cells adapt to this mathematical disadvantage by increased glucose up-take, which in turn facilitates a higher rate of glycolysis. Apart from providing cellular energy, the metabolic intermediates of glycolysis also play a pivotal role in macromolecular biosynthesis, thus conferring selective advantage to cancer cells under diminished nutrient supply. Accumulating data also indicate that intracellular ATP is a critical determinant of chemoresistance. Under hypoxic conditions where glycolysis remains the predominant energy producing pathway sensitizing cancer cells would require intracellular depletion of ATP by inhibition of glycolysis. Together, the oncogenic regulation of glycolysis and multifaceted roles of glycolytic components underscore the biological significance of tumor glycolysis. Thus targeting glycolysis remains attractive for therapeutic intervention. Several preclinical investigations have indeed demonstrated the effectiveness of this therapeutic approach thereby supporting its scientific rationale. Recent reviews have provided a wealth of information on the biochemical targets of glycolysis and their inhibitors. The objective of this review is to present the most recent research on the cancer-specific role of glycolytic enzymes including their non-glycolytic functions in order to explore the potential for therapeutic opportunities. Further, we discuss the translational potential of emerging drug candidates in light of technical advances in treatment modalities such as image-guided targeted delivery of cancer therapeutics.
760 citations