Glycolytic enzymes in non-glycolytic web: functional analysis of the key players.

To survive in the tumour microenvironment, cancer cells undergo rapid metabolic reprograming and adaptability. One of the key characteristics of cancer is increased glycolytic selectivity and decreased oxidative phosphorylation (OXPHOS). Apart from ATP synthesis, glycolysis is also responsible for NADH regeneration and macromolecular biosynthesis, such as amino acid biosynthesis and nucleotide biosynthesis. This allows cancer cells to survive and proliferate even in low-nutrient and oxygen conditions, making glycolytic enzymes a promising target for various anti-cancer agents. Oncogenic activation is also caused by the uncontrolled production and activity of glycolytic enzymes. Nevertheless, in addition to conventional glycolytic processes, some glycolytic enzymes are involved in non-canonical functions such as transcriptional regulation, autophagy, epigenetic changes, inflammation, various signaling cascades, redox regulation, oxidative stress, obesity and fatty acid metabolism, diabetes and neurodegenerative disorders, and hypoxia. The mechanisms underlying the non-canonical glycolytic enzyme activities are still not comprehensive. This review summarizes the current findings on the mechanisms fundamental to the non-glycolytic actions of glycolytic enzymes and their intermediates in maintaining the tumor microenvironment.

Cellular, Biophysical and in Silico Binding Study of ß-Estradiol-6-one 6- (O-carboxy methyl Oxime) with Tubulin in Search of Antimitotic Derivative of 2-Methoxy Estradiol.

The tubulin-microtubule system is a major target for a variety of small molecules which can interfere in cell cycle progression. Therefore, it serves as a prospective to control the incessant division of cancer cells. To identify novel inhibitors of the tubulin-microtubule system, a group of estrogen derivatives has been tested with tubulin as a target since literature surveys portray coveted behaviour from the same. Out of them, ß-Estradiol-6-one 6- (O-carboxy methyl Oxime) abbreviated as Oxime, disrupts the cytoskeleton network and induces apoptosis with nuclei fragmentation. It has been revealed from the work that Oxime targets the colchicine binding site and binds tubulin in an entropy-driven manner. This suggests that structural variation might play a key role in modulating the anti-mitotic role of estrogen derivatives. Our work reveals that Oxime might serve as a lead molecule to nurture anti-cancer research, having the potential for recovery of the vast cancer population.