PMID- 21048308
OWN - NLM
STAT- MEDLINE
DCOM- 20110629
LR  - 20220726
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 33
IP  - 11
DP  - 2010
TI  - 1,2,3,4,6-Penta-O-galloly-beta-D-glucose suppresses hypoxia-induced accumulation 
      of hypoxia-inducible factor-1alpha and signaling in LNCaP prostate cancer cells.
PG  - 1835-40
AB  - Hypoxia is the hallmark of solid tumors and contributes to tumor angiogenesis 
      mainly through activation of the transcription factor hypoxia-inducible factor-1 
      (HIF-1). In addition to upregulating vascular endothelial growth factor (VEGF) in 
      angiogenesis, HIF-1 plays critical roles in the metabolism, proliferation, 
      metastasis, and differentiation of cancer cells. We and others have previously 
      shown that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) from Oriental herbal 
      medicine possesses anti-angiogenic, anti-tumorigenic, and anti-diabetic 
      activities. In the present study, we report that PGG inhibits hypoxia-induced 
      protein accumulation, transcriptional activation, and mRNA expression of HIF-1alpha 
      in LNCaP prostate cancer cells. PGG reduced cellular and secreted VEGF levels as 
      well as mRNA expression in LNCaP cells. PGG suppressed capillary tube formation 
      in human umbilical vein endothelial cells (HUVECs) maintained in conditioned 
      medium of hypoxia-induced LNCaP cells, indicating that PGG has anti-angiogenic 
      activity under hypoxic condition. Furthermore, PGG reduced expression of 
      phosphoinositide 3-kinase (PI3K) as well as phosphorylation of AKT and mammalian 
      target of rapamycin (mTOR), but not extracellular signal-regulated kinase (ERK) 
      in LNCaP cells under hypoxic condition. Consistently, LY294002, a specific PI3K 
      inhibitor, enhanced the inactivation of HIF-1alpha and AKT by PGG in LNCaP cells. 
      Taken together, our results demonstrate that PGG inhibits hypoxia-mediated 
      accumulation of HIF-1alpha as well as its downstream signaling to VEGF and 
      PI3K/AKT/mTOR pathway in LNCaP prostate cancer cells.
FAU - Park, Ki-Young
AU  - Park KY
AD  - College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
FAU - Lee, Hyo-Jeong
AU  - Lee HJ
FAU - Jeong, Soo-Jin
AU  - Jeong SJ
FAU - Lee, Hyo-Jung
AU  - Lee HJ
FAU - Kim, Hyun-Seok
AU  - Kim HS
FAU - Kim, Sun-Hyung
AU  - Kim SH
FAU - Lim, Sabina
AU  - Lim S
FAU - Kim, Ho-Cheol
AU  - Kim HC
FAU - Lu, Junxuan
AU  - Lu J
FAU - Kim, Sung-Hoon
AU  - Kim SH
LA  - eng
GR  - R01 CA136953/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Hydrolyzable Tannins)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Plant Extracts)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 3UI3K8W93I (pentagalloylglucose)
RN  - EC 2.7.1.67 (1-Phosphatidylinositol 4-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - 1-Phosphatidylinositol 4-Kinase/metabolism
MH  - Angiogenesis Inhibitors/*pharmacology/therapeutic use
MH  - Antineoplastic Agents, Phytogenic/*pharmacology/therapeutic use
MH  - Capillaries/drug effects
MH  - Cell Line, Tumor
MH  - Endothelial Cells/drug effects
MH  - Endothelium, Vascular/drug effects/metabolism
MH  - Humans
MH  - Hydrolyzable Tannins/*pharmacology/therapeutic use
MH  - *Hypoxia
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Male
MH  - Phosphorylation
MH  - Phytotherapy
MH  - Plant Extracts/*pharmacology/therapeutic use
MH  - Prostatic Neoplasms/*drug therapy/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Umbilical Veins
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
EDAT- 2010/11/05 06:00
MHDA- 2011/06/30 06:00
CRDT- 2010/11/05 06:00
PHST- 2010/11/05 06:00 [entrez]
PHST- 2010/11/05 06:00 [pubmed]
PHST- 2011/06/30 06:00 [medline]
AID - JST.JSTAGE/bpb/33.1835 [pii]
AID - 10.1248/bpb.33.1835 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2010;33(11):1835-40. doi: 10.1248/bpb.33.1835.