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

BMC Cancer

Research Article

Joo-Seok Kim¹  Myoung-Sun Lee²  Seon-Ok Lee²  Hyo-Jeong Lee³ 

[1] College of Korean Medicine, Kyung Hee University, 1Hoegi-dong, 130-701, Dongdaemun-gu, Seoul, Republic of Korea;Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea;Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, Seoul, Republic of Korea;College of Korean Medicine, Kyung Hee University, 1Hoegi-dong, 130-701, Dongdaemun-gu, Seoul, Republic of Korea;Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, Seoul, Republic of Korea;College of Korean Medicine, Kyung Hee University, 1Hoegi-dong, 130-701, Dongdaemun-gu, Seoul, Republic of Korea;Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea;

关键词: Hypoxia;    Pristimerin;    SPHK-1;    Prostate cancer;    HIF-1α;   

DOI  :  10.1186/s12885-016-2730-2

 received in 2016-04-21, accepted in 2016-08-19,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHypoxia 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.MethodsTo 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.ResultsPristimerin 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.ConclusionTaken together, these findings suggest that pristimerin can exert an anti-cancer activity by inhibiting HIF-1α through the SPHK-1 pathway.

【 授权许可】

CC BY   
© The Author(s). 2016