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Sphingosine Kinase-1 Involves the Inhibitory Action of HIF-1α by Chlorogenic Acid in Hypoxic DU145 Cells
- Source :
- International Journal of Molecular Sciences; Volume 18; Issue 2; Pages: 325, International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 18, Iss 2, p 325 (2017)
- Publication Year :
- 2017
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2017.
-
Abstract
- Hypoxia enhances cancer development in a solid tumor. Hypoxia-inducible factor-1 α (HIF-1α) is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor that regulates tumor. HIF-1α regulates several target genes involved in many aspects of cancer progression, including angiogenesis, metastasis, anti-apoptosis and cell proliferation as well as imparts resistance to cancer treatment. In this study, we assessed Crataegus Pinnatifida Bunge var. typical Schneider ethanol extract (CPE) for its anti-cancer effects in hypoxia-induced DU145 human prostate cancer cell line. CPE decreased the abundance of HIF-1α and sphingosine kinase-1 (SPHK-1) in hypoxia-induced prostate cancer DU145 cells. CPE decreased HIF-1α and SPHK-1 as well as SPHK-1 activity. Chlorogenic acid (CA) is one of four major compounds of CPE. Compared to CPE, CA significantly decreased the expression of HIF-1α and SPHK-1 as well as SPHK-1 activity in hypoxia-induced DU145 cells. Furthermore, CA decreased phosphorylation AKT and GSK-3β, which are associated with HIF-1α stabilization and affected SPHK-1 in a concentration-dependent manner. We confirmed the mechanism of CA-induced inhibition of HIF-1α by SPHK-1 signaling pathway using SPHK-1 siRNA and SPHK inhibitor (SKI). CA decreased the secretion and cellular expression of VEGF, thus inhibiting hypoxia-induced angiogenesis. Treatment of DU145cells with SPHK1 siRNA and CA for 48 h decreased cancer cell growth, and the inhibitory action of SPHK siRNA and CA on cell growth was confirmed by decrease in the abundance of Proliferating cell nuclear antigen (PCNA).
- Subjects :
- 0301 basic medicine
Angiogenesis
chlorogenic acid
Biology
Catalysis
Article
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
DU145
Cell Line, Tumor
sphingosine kinase-1
hypoxia
prostate cancer
Humans
Physical and Theoretical Chemistry
Phosphorylation
lcsh:QH301-705.5
Molecular Biology
Protein kinase B
Spectroscopy
Cell Proliferation
Glycogen Synthase Kinase 3 beta
Sphingosine
Neovascularization, Pathologic
Cell growth
Plant Extracts
Protein Stability
Organic Chemistry
General Medicine
Hypoxia-Inducible Factor 1, alpha Subunit
Computer Science Applications
Enzyme Activation
Phosphotransferases (Alcohol Group Acceptor)
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Biochemistry
Sphingosine kinase 1
030220 oncology & carcinogenesis
Cancer cell
Cancer research
biology.protein
Signal transduction
Proto-Oncogene Proteins c-akt
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 18; Issue 2; Pages: 325
- Accession number :
- edsair.doi.dedup.....4e07b50721ee1c128c64e0c31c907256
- Full Text :
- https://doi.org/10.3390/ijms18020325