Gensenoside Rg3 Inhibits Hypoxia-induced VEGF Expression in Human Cancer Cells

Chen, Qingjiang; Zhang, Mingzhi; Wang, Lexin

doi:10.1159/000323994

Cited by 71 publications

(57 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study, we found 20(S)-Rg3 could block ovarian cancer invasion and migration by suppressing HIF-1α protein expression with no effect on mRNA level, and we confirmed 20(S)-Rg3 promoted proteasomal degradation of HIF-1α using 26S proteasome-specific PI MG132. Chen et al 25 also discovered that Rg3 facilitates HIF-1α protein degradation and shortens the half-life of HIF-1α protein significantly in human esophageal carcinoma cell line Eca-109, which was consistent with our result. 20(S)-Rg3 was proved to prevent ovarian cancer growth and intraperitoneal dissemination in nude mice in our previous study (data not shown) and weakened HIF-1α level in vivo.…”

Section: Discussionsupporting

confidence: 92%

Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals

et al. 2017

View full text Add to dashboard Cite

Hypoxia-inducible factor 1 is believed to play a prominent role in the survival and developing progress of cancers. As a result, inhibiting α subunit of hypoxia-inducible factor 1 represents an attractive strategy against tumor. Although hypoxia-inducible factor 1α is a hypoxia-regulated subunit, increasing evidence indicates that hypoxia-inducible factor 1α could stable expression under normoxic conditions, regulated by non-hypoxia-mediated mechanisms. However, there are few strategies to target hypoxia-inducible factor 1α under normoxic conditions. Here, we report that ginsenoside 20(S)-Rg3, one of the main active ingredients in red ginseng, restrains hypoxia-inducible factor 1α expression under normal oxygen levels in human ovarian cancer cell lines, SKOV3 and 3AO, which leads to potently inhibits migration of ovarian cancer in vitro and in vivo. 20(S)-Rg3 could decrease the expression of hypoxia-inducible factor 1α by upregulation of prolyl hydroxylase domain protein 1 to promoting hypoxia-inducible factor 1α ubiquitin-proteasome degradation under normal oxygen levels. Furthermore, 20(S)-Rg3 could attenuate the expression of nuclear factor-κ B, which may be another possible mechanism for 20(S)-Rg3 to block ovarian cancer migration. Taken together, our study suggests that 20(S)-Rg3 is a strong inhibitor of hypoxia-inducible factor 1α, which may provide a novel agent for future treatments for ovarian cancer.

show abstract

Section: Discussionsupporting

confidence: 92%

Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The blue formazan produced was solubilized with dimethyl sulfoxide (DMSO, 200 µl/well), and the absorbance was measured at 570 nm by a spectrophotometer. The inhibition of cell growth was calculated according to a published formula [26]. …”

Section: Methodsmentioning

confidence: 99%

Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells

Sun¹,

Cai²,

Liu³

2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal pigmented epithelial (RPE) cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells. Methods: D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002). The anti-proliferative effect of celecoxib was assessed using the MTT assay. RT-PCR, Western blotting and ELISA were performed to detect the levels of PI3K, phosphorylated AKT (p-AKT), HIF-1α, VEGF and COX-2. Results: Celecoxib inhibited the proliferation of RPE cells in a dose-dependent manner. Celecoxib suppressed the expression of VEGF at both the mRNA and protein levels and decreased HIF-1α protein expression. HIF-1α activation was regulated by the PI3K/AKT pathway. The celecoxib-induced down-regulation of HIF-1α and VEGF required the suppression of the hypoxia-induced PI3K/AKT pathway. However, the down-regulation of COX-2 did not occur in cells treated with celecoxib. Conclusions: The antiangiogenic effects of celecoxib in RPE cells under hypoxic conditions resulted from the inhibition of HIF-1α and VEGF expression, which may be partly mediated by a COX-2-independent, PI3K/AKT-dependent pathway.

show abstract

“…An enzyme-linked immunoassay analyzer determined the absorbance of each well at 490 nm (A490). The inhibition rates of cell growth were calculated based on a published formula [16].…”

Section: -(4 5-dimethylthazol-2-yl)-2 5-diphenyltetrazolium Bromidmentioning

confidence: 99%

The Effect and Mechanism of Celecoxib in Hypoxia-Induced Survivin Up-Regulation in HUVECs

Liu

Zhao

Cai

2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: To investigate the roles of hypoxia-inducible factor 1α (HIF-1α), cyclooxygenase-2 (Cox-2) and its product, Prostaglandin E2 (PGE₂), in the mechanisms underlying hypoxia-induced survivin expression in human umbilical vein endothelial cells (HUVECs) and to examine the effect of celecoxib, a selective Cox-2 inhibitor, on survivin expression. Methods: HUVECs were exposed to a normal (95% O₂) or hypoxic (3% O₂) environment for 24 hrs. We observed the localized expression of survivin, Cox-2 and HIF-1α in HUVECs using immunocytochemistry and detected the inhibitory effects of celecoxib on the growth of HUVECs using an MTT assay. mRNA and protein levels of Cox-2, HIF-1α and survivin were determined by real-time PCR and Western blot analysis under hypoxic conditions for 0, 6, 12, or 24 hrs. The time course changes of HIF-1α and survivin protein expression induced by cobalt chloride (CoCl₂) were studied using Western blot analysis. We then treated HUVECs under hypoxia for 24 hrs with celecoxib (a Cox-2 selective inhibitor), genistein (a HIF-1α inhibitor) or exogenous PGE₂ to further investigate the changes in hypoxia-induced survivin expression. Results: Following 24 hrs of hypoxic treatment, cells exhibited strongly positive survivin, HIF-1α and Cox-2 cytoplasmic staining. Celecoxib (65 μM) effectively inhibited cell proliferation under hypoxic conditions. The protein and mRNA levels of Cox-2, HIF-1α and survivin were increased under hypoxia. The patterns of HIF-1α and survivin expression induced by CoCl₂ were similar to those induced by exposure to hypoxia. Genistein partially blocked survivin expression. Celecoxib reversed the hypoxia-induced survivin expression, whereas the addition of PGE₂ partially restored this effect. Conclusions: Hypoxia-induced survivin expression in HUVECs may be mediated by dual interdependent mechanisms directly involving HIF-1α and indirectly involving the Cox-2/PGE₂ pathways. Celecoxib may offset hypoxia-induced survivin expression.

show abstract

Gensenoside Rg3 Inhibits Hypoxia-induced VEGF Expression in Human Cancer Cells

Cited by 71 publications

References 42 publications

Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals

Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals

Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells

The Effect and Mechanism of Celecoxib in Hypoxia-Induced Survivin Up-Regulation in HUVECs

Contact Info

Product

Resources

About