Therapeutic impact of Nano diosgenin on metabolic reprogramming in an animal model of mammary oncogenesis via modulating carbohydrate metabolizing enzymes

Abstract

Objectives: The primary target of this study is to explore a novel therapeutic pathway of nano Diosgenin (DG) by pin-pointing the metabolic enzymes that underlies its anti-breast cancer impacts. Methods: A single dosage of 7.12 Dimethyl Benz(a)anthracene (DMBA) (25 mg/kg b.wt) was injected to induce breast cancer. Oral administration of DG (10 mg/kg b.wt) and DG encapsulated chitosan nanoparticle (DG@CS-NP) (5 mg/kg b.wt) was used to medicate DMBA induced tumor bearing rats just after the emergence of a tumor. After the experimental period, biochemical analyses were carried out. Results: Mammary carcinoma bearing rats showed a significant rise in the levels of glycolytic enzymes (hexokinase, phosphoglucoisomerase, and aldolase) and the pentose phosphate pathway enzyme (glucose-6-phosphate dehydrogenase). It also elicits a drop in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1, 6- diphosphatase) and mitochondrial enzymes (succinate dehydrogenase and malate dehydrogenase). Contrarily, nano DG dramatically reverted the rates of glycolytic enzymes, pentose phosphate pathway enzymes, gluconeogenic enzymes, and mitochondrial enzymes in the mammary, liver and kidney tissues to near normal tiers on compared to plain DG treated rats. Thereby, confirming its chemotherapeutic prospects on metabolic rewiring. Conclusion: Thus, our observations suggested that nano DG is a potent therapeutic agent that might have a significant influence on metabolic complications of breast cancer than free DG.