Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro.
Overexpression of hypoxia-inducible factor-1 (HIF-1) α, a transcription factor which immortalizes tumors by inducing expression of the genes involved in cell survival, migration and angiogenesis, is closely associated with poor prognosis, increased risk of metastasis and increased mortality. Oligomer procyanidins (F2), a natural fraction from grape seeds, has been demonstrated to have antioxidant and antitumor activities, however the antitumor effect of F2 targeting HIF-1α remains unknown. The present study showed that F2 markedly decreased HIF-1α and the expression of its target genes in cancer cells through inactivating the EGFR-PI3K-AKT-mTOR and MAPK-ERK1/2 pathways. Moreover, F2 suppressed vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 expressions, followed by the inhibition of tumor angiogenesis and cell invasion in a HIF-1α-dependent manner. Collectively, these findings indicate that the antitumor effect of F2 is, at least in part, mediated by suppressing HIF-1α-dependent pathway, and suggest that F2 may be a potentially useful agent for treatment of human cancer.
Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Hong Li
HL
Zheng
Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Jingyu
J
Yang
Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Yue
Y
Hou
Department of Drug Analysis, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Baoshan
B
Sun
Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Qingchun
Q
Zhang
Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Yanhua
Y
Mou
Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Lihui
L
Wand
Department of Pharmacology, Shenyang Pharmaceutical University, Shenhe District, 110016 Shenyang, P.R. China.
Chunfu
C
Wu
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001254:Astrocytoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056604:Grape Seed Extract / Q000008:administration & dosage; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D044945:Proanthocyanidins / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D056604:Grape Seed Extract; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D044945:Proanthocyanidins