Assessing the anticancer effects of Metformin

Metformin is an anti-hyperglycemic biguanide drug that is widely used as
the first-line prescription for managing type 2 Diabetes Mellitus (T2DM).
Research suggests 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. Suggested biological means that metformin
utilizes include AMPK-driven cascades involving two pathways, a direct and
an indirect one. This leads to a decrease in the mechanistic activity of
rapamycin (mTOR), folate level, c-MYC, NF-B, and also increases P53
phosphorylation. These cascades will also decrease cyclin D1, reactive
oxygen species (ROS), and increase mTOR Complex1 (mTORC1) concentrations,
apoptosis, and autophagy. Some researchers suggest metformin also exerts
anti-inflammatory effects through reducing Interleukins-6 (IL6) and 8
(IL8), inhibition of protein translation via LKB1, increasing expression
of GPD1 which suppresses cancer by inhibiting mitochondria and inducing
cell apoptosis, and inhibiting leptin while increasing adiponectin
production. There is also evidence of possible suppressive effects on
overexpressed signals in some cancers, such as Notch1/Hes1, STAT3, and
HER2+ which ultimately could increase survival rates in cancer patients.
Our goal is to explore the mechanisms in which metformin can act as an
anticancer drug and assess the effect of metformin on various types of
malignancies. We retrospectively studied 266 cancer patients diagnosed in
2018 – 2019 in King Fahd Hospital of the University (KFHU). This
population was furtherly divided into non-diabetic and diabetic cancer
patients and the latter group into those who received metformin and those
who did not. The results showed the statistical significance of metformin
use on the cancer grade at diagnosis that favourably influences the
morbidity/mortality. 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.