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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells

Authors: Seon-Ok Lee, Joo-Seok Kim, Myoung-Sun Lee, Hyo-Jeong Lee

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Hypoxia is a typical character of locally advanced solid tumours. The transcription factor hypoxia-inducible factor 1α (HIF-1α) is the main regulator under the hypoxic environment. HIF-1α regulates various genes to enhance tumour progression, angiogenesis, and metastasis. Sphingosine kinase 1 (SPHK-1) is a modulator of HIF-1α.

Methods

To investigate the molecular mechanisms of pristimerin in association with SPHK-1 pathways in hypoxic PC-3 cancer cells. Vascular endothelial growth factor (VEGF) production, cell cycles, and SPHK-1 activity were measured, and western blotting, an MTT assay, and an RNA interference assay were performed.

Results

Pristimerin inhibited HIF-1α accumulation in a concentration- and-time-dependent manner in hypoxic PC-3 cells. Pristimerin suppressed the expression of HIF-1α by inhibiting SPHK-1. Moreover, inhibiting SPHK-1 with a sphingosine kinase inhibitor enhanced the suppression of HIF-1α, phosphorylation AKT, and glycogen synthase kinase-3β (GSK-3β) by pristimerin under hypoxia. Furthermore, a reactive oxygen species (ROS) scavenger enhanced the inhibition of HIF-1α and SPHK-1 by pristimerin.

Conclusion

Taken together, these findings suggest that pristimerin can exert an anti-cancer activity by inhibiting HIF-1α through the SPHK-1 pathway.
Appendix
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Metadata
Title
Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells
Authors
Seon-Ok Lee
Joo-Seok Kim
Myoung-Sun Lee
Hyo-Jeong Lee
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2730-2

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