Cancer and diabetes: the interlinking metabolic pathways and repurposing actions of antidiabetic drugs

Abstract

Cancers are regarded as one of the main causes of death and result in high health burden worldwide. The management of cancer include chemotherapy, surgery and radiotherapy. The chemotherapy, which involves the use of chemical agents with cytotoxic actions is utilised as a single treatment or combined treatment. However, these managements of cancer such as chemotherapy poses some setbacks such as cytotoxicity on normal cells and the problem of anticancer drug resistance. Therefore, the use of other therapeutic agents such as antidiabetic drugs is one of the alternative interventions used in addressing some of the limitations in the use of anticancer agents. Antidiabetic drugs such as sulfonylureas, biguanides and thiazolidinediones showed beneficial and repurposing actions in the management of cancer, thus, the activities of these drugs against cancer is attributed to some of the metabolic links between the two disorders and these includes hyperglycaemia, hyperinsulinemia, inflammation, and oxidative stress as well as obesity. Furthermore, some studies showed that the use of antidiabetic drugs could serve as risk factors for the development of cancerous cells particularly pancreatic cancer. However, the beneficial role of these chemical agents overweighs their detrimental actions in cancer management. Hence, the present review indicates the metabolic links between cancer and diabetes and the mechanistic actions of antidiabetic drugs in the management of cancers.

Glutor, a Glucose Transporter Inhibitor, Exerts Antineoplastic Action on Tumor Cells of Thymic Origin: Implication of Modulated Metabolism, Survival, Oxidative Stress, Mitochondrial Membrane Potential, pH Homeostasis, and Chemosensitivity

“…Moreover, hypoglycemia caused by impaired glucose uptake could be another trigger for induction of apoptosis. Hypoglycemia has been demonstrated to cause a decrease in ATP production associated with the induction of apoptosis ( 65 , 66 ). Our experimental findings do not indicate a direct implication of glutor in the modulation of mitochondrial functions such as mitochondrial membrane potential; however, our results suggest the role of glutor-modulated p53 expression in the implication of altered mitochondrial membrane polarization.…”

DPP4 Regulates DHCR24-Mediated Cholesterol Biosynthesis to Promote Methotrexate Resistance in Gestational Trophoblastic Neoplastic Cells

“…Metabolic reprogramming is a hallmark of both diabetes and cancer, which is presented with similar abnormalities in glucose, fatty acid, and cholesterol metabolisms ( 46 ). DPP4 has been identified as a potential regulator that links enhanced cancer risk with metabolic diseases such as hyperglycemia and obesity ( 47 ).…”

Critical material designs for mucus- and mucosa-penetrating oral insulin nanoparticle development

“…As insulin is a growth factor, the unabsorbed insulin poses health risks. It can promote tumor development in the colon through activating the RAS-MAPK and PI3K-AKT-mTOR signalling pathways which are associated with tumor proliferation, epithelial–mesenchymal transition and survival [105,106]. Epidemiological and preclinical studies have indicated that hyperinsulinemia plays a role in the development of cancer.…”