Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity
and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic
agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin
towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few
studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review
aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the
absence of diabetes mellitus. In CRC-independent of diabetes mellitus, highly deregulation of
PI3K/AKT pathway is found which activates the downstream mammalian target of rapamycin (mTOR).
Metformin inhibits cancer growth in colon by suppressing the colonic epithelial proliferation by inhibiting
the mTOR pathway. Metformin exerts its anti-neoplastic effects by acting on tumour suppressor
pathway via activating the adenosine monophosphateactivated protein kinase (AMPK) signaling
pathway. Metformin interrupts the glucose metabolism by activating the AMPK. Metformin reduces
tumour cell growth and metastasis by activating the p53 tumour suppressor gene. In addition to its
therapeutic benefits, metformin is easily accessible, cost effective with better tolerance to the patients
compared to the chemotherapeutic agents. This review summarised modern findings on the therapeutic
applications of metformin on the colorectal cancer with no evidences of diabetes mellitus.
Keywords: Anti-neoplastic effect, colorectal cancer, metformin, molecular pathway, non-diabetes, diabetes mellitus.
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