PMID- 25895126
OWN - NLM
STAT- MEDLINE
DCOM- 20160229
LR  - 20220330
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 13
DP  - 2015 May 10
TI  - Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: 
      similarity with calorie restriction.
PG  - 10908-23
AB  - Caloric restriction (CR) was recently demonstrated by us to restrict ovarian 
      cancer growth in vivo. CR resulted in activation of energy regulating enzymes 
      adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by 
      downstream inhibition of Akt-mTOR. In the present study, we investigated the 
      effects of metformin on ovarian cancer growth in mice fed a high energy diet 
      (HED) and regular diet (RD) and compared them to those seen with CR in an 
      immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED 
      diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking 
      water. Metformin treatment in RD and HED mice resulted in a significant reduction 
      in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by 
      decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory 
      cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet 
      mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt 
      and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing 
      effects by inducing similar metabolic changes, providing further evidence of its 
      potential not only as a therapeutic drug but also as a preventive agent.
FAU - Al-Wahab, Zaid
AU  - Al-Wahab Z
AD  - Wayne State University, Detroit, MI, USA.
FAU - Mert, Ismail
AU  - Mert I
AD  - Wayne State University, Detroit, MI, USA.
AD  - Division of Gynecologic Oncology, Department of Women's Health, Henry Ford 
      Hospital, Detroit, MI, USA.
FAU - Tebbe, Calvin
AU  - Tebbe C
AD  - Division of Gynecologic Oncology, Department of Women's Health, Henry Ford 
      Hospital, Detroit, MI, USA.
FAU - Chhina, Jasdeep
AU  - Chhina J
AD  - Division of Gynecologic Oncology, Department of Women's Health, Henry Ford 
      Hospital, Detroit, MI, USA.
FAU - Hijaz, Miriana
AU  - Hijaz M
AD  - Division of Gynecologic Oncology, Department of Women's Health, Henry Ford 
      Hospital, Detroit, MI, USA.
FAU - Morris, Robert T
AU  - Morris RT
AD  - Wayne State University, Detroit, MI, USA.
FAU - Ali-Fehmi, Rouba
AU  - Ali-Fehmi R
AD  - Department of Pathology, Karmanos Cancer Institute, Wayne State University, 
      Detroit, MI, USA.
FAU - Giri, Shailendra
AU  - Giri S
AD  - Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.
AD  - Josephine Cancer Institute, Henry Ford Hospital, Detroit, MI, USA.
FAU - Munkarah, Adnan R
AU  - Munkarah AR
AD  - Division of Gynecologic Oncology, Department of Women's Health, Henry Ford 
      Hospital, Detroit, MI, USA.
AD  - Josephine Cancer Institute, Henry Ford Hospital, Detroit, MI, USA.
FAU - Rattan, Ramandeep
AU  - Rattan R
AD  - Division of Gynecologic Oncology, Department of Women's Health, Henry Ford 
      Hospital, Detroit, MI, USA.
AD  - Josephine Cancer Institute, Henry Ford Hospital, Detroit, MI, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Anticarcinogenic Agents/*pharmacology
MH  - *Caloric Restriction
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Energy Metabolism/*drug effects
MH  - Enzyme Activation
MH  - Female
MH  - Inflammation Mediators/metabolism
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Metformin/*pharmacology
MH  - Mice, Inbred C57BL
MH  - Ovarian Neoplasms/metabolism/pathology/*prevention & control
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Time Factors
MH  - Tumor Burden
PMC - PMC4484428
OTO - NOTNLM
OT  - AMPK
OT  - calorie restriction
OT  - mTOR
OT  - metformin
OT  - ovarian cancer
COIS- CONFLICTS OF INTEREST Authors have no conflicts of interest to report.
EDAT- 2015/04/22 06:00
MHDA- 2016/03/02 06:00
PMCR- 2015/05/10
CRDT- 2015/04/21 06:00
PHST- 2015/02/05 00:00 [received]
PHST- 2015/02/23 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/03/02 06:00 [medline]
PHST- 2015/05/10 00:00 [pmc-release]
AID - 3434 [pii]
AID - 10.18632/oncotarget.3434 [doi]
PST - ppublish
SO  - Oncotarget. 2015 May 10;6(13):10908-23. doi: 10.18632/oncotarget.3434.