PMID- 21133850
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20211020
IS  - 1873-4316 (Electronic)
IS  - 1389-2010 (Print)
IS  - 1389-2010 (Linking)
VI  - 14
IP  - 3
DP  - 2013
TI  - Peroxisome proliferator activated receptor alpha ligands as anticancer drugs 
      targeting mitochondrial metabolism.
PG  - 342-56
AB  - Tumor cells show metabolic features distinctive from normal tissues, with 
      characteristically enhanced aerobic glycolysis, glutaminolysis and lipid 
      synthesis. Peroxisome proliferator activated receptor alpha (PPAR alpha) is activated by 
      nutrients (fatty acids and their derivatives) and influences these metabolic 
      pathways acting antagonistically to oncogenic Akt and c-Myc. Therefore PPAR alpha can 
      be regarded as a candidate target molecule in supplementary anticancer 
      pharmacotherapy as well as dietary therapeutic approach. This idea is based on 
      hitting the cancer cell metabolic weak points through PPAR alpha mediated stimulation 
      of mitochondrial fatty acid oxidation and ketogenesis with simultaneous reduction 
      of glucose and glutamine consumption. PPAR alpha activity is induced by fasting and 
      its molecular consequences overlap with the effects of calorie restriction and 
      ketogenic diet (CRKD). CRKD induces increase of NAD+/NADH ratio and drop in 
      ATP/AMP ratio. The first one is the main stimulus for enhanced protein 
      deacetylase SIRT1 activity; the second one activates AMP-dependent protein kinase 
      (AMPK). Both SIRT1 and AMPK exert their major metabolic activities such as fatty 
      acid oxidation and block of glycolysis and protein, nucleotide and fatty acid 
      synthesis through the effector protein peroxisome proliferator activated receptor 
      gamma 1 alpha coactivator (PGC-1alpha). PGC-1alpha cooperates with PPAR alpha and their 
      activities might contribute to potential anticancer effects of CRKD, which were 
      reported for various brain tumors. Therefore, PPAR alpha activation can engage 
      molecular interplay among SIRT1, AMPK, and PGC-1alpha that provides a new, low 
      toxicity dietary approach supplementing traditional anticancer regimen.
FAU - Grabacka, Maja
AU  - Grabacka M
AD  - Department of Food Biotechnology, Faculty of Food Technology, University of 
      Agriculture, Krakow 30- 149, ul. Balicka 122, Poland. maja.grabacka@ur.krakow.pl
FAU - Pierzchalska, Malgorzata
AU  - Pierzchalska M
FAU - Reiss, Krzysztof
AU  - Reiss K
LA  - eng
GR  - R01 CA095518/CA/NCI NIH HHS/United States
GR  - R01 CA095518-10/CA/NCI NIH HHS/United States
GR  - R01 CA 095518/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Curr Pharm Biotechnol
JT  - Current pharmaceutical biotechnology
JID - 100960530
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Ligands)
RN  - 0 (PPAR alpha)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Humans
MH  - Ligands
MH  - Mitochondria/*metabolism
MH  - Neoplasms/*metabolism
MH  - PPAR alpha/*metabolism
MH  - Sirtuins/metabolism
PMC - PMC3631438
MID - NIHMS279565
EDAT- 2010/12/08 06:00
MHDA- 2013/10/18 06:00
PMCR- 2013/04/20
CRDT- 2010/12/08 06:00
PHST- 2010/04/22 00:00 [received]
PHST- 2010/07/15 00:00 [revised]
PHST- 2010/09/17 00:00 [accepted]
PHST- 2010/12/08 06:00 [entrez]
PHST- 2010/12/08 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2013/04/20 00:00 [pmc-release]
AID - BSP/CPB/E-Pub/00058-12-3 [pii]
AID - 10.2174/1389201011314030009 [doi]
PST - ppublish
SO  - Curr Pharm Biotechnol. 2013;14(3):342-56. doi: 10.2174/1389201011314030009.