Assessing the anticancer effects of metformin

Abstract

Background: Metformin is an antihyperglycemic biguanide that is used as the first-line treatment for type 2 diabetes mellitus (T2DM). Metformin use helps control T2DM which is one of the many risk factors for cancer and is proposed to have multiple antagonistic actions against cancer cells. Metformin induces adenosine monophosphate-activated protein kinase (AMPK)-driven cascades, involving two pathways, a direct and an indirect one. This leads to a decrease in the mechanistic activity of mammalian target of rapamycin (mTOR), folate level, c-MYC (a family of regulator genes and proto-oncogenes), NF-κB (nuclear factor kappa of B cell), and also increases tumor suppressor P53 phosphorylation. These cascades will also decrease cyclin D1, reactive oxygen species (ROS), and increase mTOR complex1 (mTORC1) concentrations, apoptosis, and autophagy. Metformin also exerts anti-inflammatory effects through reducing interleukins 6 (IL6) and 8 (IL8), inhibition of protein translation via LKB1 (liver kinase B1), increasing expression of GPD1 (glycerol-3-phosphate dehydrogenase 1) which suppresses cancer by inhibiting mitochondria, inducing cell apoptosis, and inhibiting leptin while increasing adiponectin production.    We would like to assess the anticancer effect of metformin on various types of malignancies.  Methods:  The 266 cancer patients diagnosed in 2018–2019 in King Fahd Hospital of the University (KFHU) were divided into non-diabetic and diabetic cancer patients (with or without metformin).  The data includes age, gender, body mass index (BMI), type of cancer with grades and stages, T2DM, with or without metformin, complications, and fate etc. of each case.  Results: Out of 300, 266 were selected for the analysis. The results showed the statistical significance (p value 0.022) of metformin use on the cancer grade at diagnosis that favorably influences the morbidity/mortality.   Conclusions: Metformin might have an anti-cancer effect on the grade of cancer at the time of diagnosis regardless of its dosage, and this might improve the prognosis of malignancy.