PMID- 27919208
OWN - NLM
STAT- MEDLINE
DCOM- 20180427
LR  - 20211204
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 18
IP  - 6
DP  - 2017
TI  - Is Metformin a Therapeutic Paradigm for Colorectal Cancer: Insight into the 
      Molecular Pathway?
PG  - 734-750
LID - 10.2174/1389450118666161205125548 [doi]
AB  - 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.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Thent, Zar Chi
AU  - Thent ZC
AD  - Anatomy Discipline, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 
      Campus, Jalan Hospital, 47000, Selangor, Malaysia.
FAU - Zaidun, Nurul Hannim
AU  - Zaidun NH
FAU - Azmi, Muhammad Fairuz
AU  - Azmi MF
FAU - Senin, Mu Izuddin
AU  - Senin MI
FAU - Haslan, Haszianaliza
AU  - Haslan H
FAU - Salehuddin, Ruzain
AU  - Salehuddin R
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Antineoplastic Agents)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Cell Cycle/drug effects
MH  - Cell Proliferation/drug effects
MH  - Clinical Trials as Topic
MH  - Colorectal Neoplasms/*drug therapy/metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Metformin/*pharmacology/therapeutic use
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Anti-neoplastic effect
OT  - colorectal cancer
OT  - diabetes mellitus
OT  - metformin
OT  - molecular pathway
OT  - non-diabetes
EDAT- 2016/12/07 06:00
MHDA- 2018/04/28 06:00
CRDT- 2016/12/07 06:00
PHST- 2016/03/01 00:00 [received]
PHST- 2016/10/20 00:00 [revised]
PHST- 2016/11/24 00:00 [accepted]
PHST- 2016/12/07 06:00 [pubmed]
PHST- 2018/04/28 06:00 [medline]
PHST- 2016/12/07 06:00 [entrez]
AID - CDT-EPUB-80151 [pii]
AID - 10.2174/1389450118666161205125548 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2017;18(6):734-750. doi: 10.2174/1389450118666161205125548.