title: Is Metformin a Therapeutic Paradigm for Colorectal Cancer: Insight into the Molecular Pathway?
abstract: 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 monophosphate.activated 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.
authors.affiliation: Anatomy Discipline, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000, Selangor, Malaysia.
authors.forename: Zar Chi
authors.initials: ZC
authors.lastname: Thent
authors.forename: Nurul Hannim
authors.initials: NH
authors.lastname: Zaidun
authors.forename: Muhammad Fairuz
authors.initials: MF
authors.lastname: Azmi
authors.forename: Mu Izuddin
authors.initials: MI
authors.lastname: Senin
authors.forename: Haszianaliza
authors.initials: H
authors.lastname: Haslan
authors.forename: Ruzain
authors.initials: R
authors.lastname: Salehuddin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Anti-neoplastic effect; colorectal cancer; diabetes mellitus; metformin; molecular pathway; non-diabetes