PMID- 22223345
OWN - NLM
STAT- MEDLINE
DCOM- 20120615
LR  - 20190720
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 35
IP  - 1
DP  - 2012
TI  - Anticancer properties of pomolic acid-induced AMP-activated protein kinase 
      activation in MCF7 human breast cancer cells.
PG  - 105-10
AB  - AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found 
      in all eukaryotes. Recent studies indicate that AMPK activation strongly 
      suppresses cell proliferation in tumor cells, which requires high rates of 
      protein synthesis and de novo fatty acid synthesis for their rapid growth. 
      Pomolic acid (PA) has been previously described as being active in inhibiting the 
      growth of cancer cells. In this study, we investigated PA activated AMPK, and 
      this activity was related to proliferation and apoptosis in MCF7 breast cancer 
      cells. PA inhibited cell proliferation and induced sub-G(1) arrest, elevating the 
      mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and 
      poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK 
      activation was increased by treating cells with PA, inactivated by treating cells 
      with a compound C, and co-treatment consisting of PA and aminoimidazole 
      carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These 
      anti-cancer potentials of PA were accompanied by effects on de novo fatty acid 
      synthesis as shown by the decreased expression of fatty acid synthase, and 
      decreased acetyl-CoA carboxylase activation and incorporation of [(3)H]acetyl-CoA 
      into fatty acids. In addition, PA inhibited key enzymes involved in protein 
      synthesis such as mammalian target of rapamycin (mTOR), 70 kDa ribosomal protein 
      S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E-binding 
      protein 1 (4EBP1). These results suggest that PA exerts anti-cancer properties 
      through the modulation of AMPK pathways and its value as an anti-cancer agent in 
      breast cancer therapy.
FAU - Youn, Seog Hyeon
AU  - Youn SH
AD  - Department of Surgery, Chungnam National University Hospital, Daejeon 301-721, 
      Korea.
FAU - Lee, Jin Sun
AU  - Lee JS
FAU - Lee, Myung Sun
AU  - Lee MS
FAU - Cha, Eun Young
AU  - Cha EY
FAU - Thuong, Phuong Thien
AU  - Thuong PT
FAU - Kim, Je Ryong
AU  - Kim JR
FAU - Chang, Eil Sung
AU  - Chang ES
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Fatty Acids)
RN  - 0 (Plant Extracts)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 60HAB1ZK1T (pomolic acid)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 2.3.1.85 (Fatty Acid Synthases)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Acetyl-CoA Carboxylase/metabolism
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Antineoplastic Agents, Phytogenic/pharmacology/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/metabolism
MH  - Caspase 3/metabolism
MH  - Caspase 9/metabolism
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism
MH  - Enzyme Activation/drug effects
MH  - Fatty Acid Synthases/metabolism
MH  - Fatty Acids/biosynthesis
MH  - Female
MH  - G1 Phase/drug effects
MH  - Gene Expression/drug effects
MH  - Genes, p53
MH  - Humans
MH  - Oleanolic Acid/*analogs & derivatives/pharmacology/therapeutic use
MH  - *Phytotherapy
MH  - Plant Extracts/pharmacology/*therapeutic use
MH  - Poly(ADP-ribose) Polymerases/drug effects
MH  - Protein Biosynthesis/drug effects
MH  - RNA, Messenger/metabolism
MH  - Ribonucleotides/pharmacology
EDAT- 2012/01/10 06:00
MHDA- 2012/06/16 06:00
CRDT- 2012/01/07 06:00
PHST- 2012/01/07 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/06/16 06:00 [medline]
AID - JST.JSTAGE/bpb/35.105 [pii]
AID - 10.1248/bpb.35.105 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2012;35(1):105-10. doi: 10.1248/bpb.35.105.