PMID- 34139918
OWN - NLM
STAT- MEDLINE
DCOM- 20220406
LR  - 20220406
IS  - 2038-2529 (Electronic)
IS  - 0300-8916 (Linking)
VI  - 108
IP  - 2
DP  - 2022 Apr
TI  - Multidimensional mechanisms of metformin in cancer treatment.
PG  - 111-118
LID - 10.1177/03008916211023548 [doi]
AB  - Metformin has been in clinical use for more than half a century, yet its 
      molecular mechanism of action is not entirely understood. Metformin has been 
      shown to have antiproliferative and synergistic effects on various types of 
      cancers. The anticancer effects of metformin are potentially applicable to both 
      diabetic and nondiabetic patients. Areas of ongoing investigation focus on 
      metformin's ability to activate adenosine monophosphate kinase (AMPK), in 
      addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), 
      hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and 
      human epidermal growth factor receptor 2 (HER2). Additional anticancer effects 
      are exhibited by acting on liver kinase B1 (LKB1), CREB-regulated transcription 
      coactivator 2 (CRTC2), nitric oxide, and reactive oxygen species. Further 
      investigation will be focused on elucidating metformin's metal-binding properties 
      and how they may be harnessed for their anticancer effect. The acquired knowledge 
      about metformin properties has expanded the number of targets for drug discovery 
      such as microRNA, hexokinase, adenylate cyclase, transcription factors, various 
      cyclins, and copper. In order to design anticancer drugs that mimic metformin's 
      mechanism of action, binding assay studies must be conducted to fully understand 
      and utilize the AMPK-dependent and independent mechanisms. Metformin's complex 
      mechanisms that can potentially make this drug a multifaceted therapy targeting 
      tumorigenesis in addition to information from ongoing clinical trials implicate 
      that metformin can be a potential chemotherapeutic drug or adjuvant that could 
      prove to be vital to future strategies against several types of cancer.
FAU - Singh-Makkar, Sarabjot
AU  - Singh-Makkar S
AD  - Division of Research & Academic Affairs, Larkin Community Hospital, South Miami, 
      FL, USA.
FAU - Pandav, Krunal
AU  - Pandav K
AUID- ORCID: 0000-0002-5451-7115
AD  - Division of Research & Academic Affairs, Larkin Community Hospital, South Miami, 
      FL, USA.
FAU - Hathaway, Donald 3rd
AU  - Hathaway D 3rd
AUID- ORCID: 0000-0002-1613-6362
AD  - Division of Research & Academic Affairs, Larkin Community Hospital, South Miami, 
      FL, USA.
FAU - Paul, Trissa
AU  - Paul T
AUID- ORCID: 0000-0002-2884-5756
AD  - Division of Research & Academic Affairs, Larkin Community Hospital, South Miami, 
      FL, USA.
FAU - Youssef, Pamela
AU  - Youssef P
AD  - Neuroscience Department, Larkin University, Miami, FL, USA.
LA  - eng
PT  - Journal Article
DEP - 20210618
PL  - United States
TA  - Tumori
JT  - Tumori
JID - 0111356
RN  - 0 (Antineoplastic Agents)
RN  - 0 (MicroRNAs)
RN  - 0 (Reactive Oxygen Species)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - *Antineoplastic Agents/pharmacology/therapeutic use
MH  - Humans
MH  - *Metformin/pharmacology/therapeutic use
MH  - *MicroRNAs
MH  - *Neoplasms/drug therapy
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - HER2
OT  - MTOR
OT  - Metformin
OT  - Myc mRNA
EDAT- 2021/06/19 06:00
MHDA- 2022/04/07 06:00
CRDT- 2021/06/18 05:31
PHST- 2021/06/19 06:00 [pubmed]
PHST- 2022/04/07 06:00 [medline]
PHST- 2021/06/18 05:31 [entrez]
AID - 10.1177/03008916211023548 [doi]
PST - ppublish
SO  - Tumori. 2022 Apr;108(2):111-118. doi: 10.1177/03008916211023548. Epub 2021 Jun 
      18.