PMID- 33617821
OWN - NLM
STAT- MEDLINE
DCOM- 20210518
LR  - 20210518
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 897
DP  - 2021 Apr 15
TI  - Pharmacologic mechanisms underlying antidiabetic drug metformin's chemopreventive 
      effect against colorectal cancer.
PG  - 173956
LID - S0014-2999(21)00109-6 [pii]
LID - 10.1016/j.ejphar.2021.173956 [doi]
AB  - In this review, current data was used to elucidate the mechanisms by which 
      metformin hydrochloride exerts chemopreventive effects on colorectal cancer 
      (CRC). The first-line agent for the treatment of type 2 diabetes mellitus (T2DM), 
      metformin, has recently been cited in a number of studies, in-vitro and in-vivo, 
      for its potential anticancer capabilities in a variety of malignancies. While 
      generally known to target AMP-activated protein kinase (AMPK), as an antidiabetic 
      agent, the mechanisms by which metformin confers anticancer properties, 
      particularly in CRC, are far less understood. This review aims to comprehensively 
      integrate novel pharmacologic findings, especially more recent insights, to 
      explain metformin's anti-CRC mechanisms. Among these include metformin-mediated 
      alterations to a number of key signaling pathways involving CRC cell growth and 
      stemness, anti-EMT (epithelial-mesenchymal transition) regulatory actions, as 
      well as altered pro-cancer cellular energetic states and survival. These findings 
      may prove particularly meaningful in the fields of experimental and clinical 
      oncotherapy.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Jaromy, Michelle
AU  - Jaromy M
AD  - Department of Pharmacological Sciences, Stony Brook University, 100 Nicolls Rd, 
      Stony Brook, NY, 11794, USA. Electronic address: 
      Michelle.Jaromy@alumni.stonybrook.edu.
FAU - Miller, Joshua D
AU  - Miller JD
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Renaissance 
      School of Medicine at Stony Brook University, 100 Nicolls Rd, Stony Brook, NY, 
      11794, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210219
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Anticarcinogenic Agents/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Transformation, Neoplastic/*drug effects/metabolism/pathology
MH  - Colorectal Neoplasms/metabolism/pathology/*prevention & control
MH  - Energy Metabolism/drug effects
MH  - Epithelial-Mesenchymal Transition/drug effects
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Metformin/*pharmacology
MH  - Neoplastic Stem Cells/drug effects/metabolism/pathology
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - 4091)
OT  - Chemoprevention
OT  - Colorectal neoplasms
OT  - Diabetes mellitus
OT  - Metformin
OT  - Metformin (PubChem CID
OT  - Type 2
EDAT- 2021/02/23 06:00
MHDA- 2021/05/19 06:00
CRDT- 2021/02/22 20:10
PHST- 2020/10/01 00:00 [received]
PHST- 2021/02/12 00:00 [revised]
PHST- 2021/02/15 00:00 [accepted]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/05/19 06:00 [medline]
PHST- 2021/02/22 20:10 [entrez]
AID - S0014-2999(21)00109-6 [pii]
AID - 10.1016/j.ejphar.2021.173956 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2021 Apr 15;897:173956. doi: 10.1016/j.ejphar.2021.173956. Epub 
      2021 Feb 19.