title: Anti-cancer effect of pristimerin by inhibition of HIF-1α involves the SPHK-1 pathway in hypoxic prostate cancer cells.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Taken together, these findings suggest that pristimerin can exert an anti-cancer activity by inhibiting HIF-1α through the SPHK-1 pathway.
authors: Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, Seoul, Republic of Korea.|College of Korean Medicine, Kyung Hee University, 1Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors: Seon-Ok
authors: SO
authors: Lee
authors: College of Korean Medicine, Kyung Hee University, 1Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors: Joo-Seok
authors: JS
authors: Kim
authors: Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, Seoul, Republic of Korea.|College of Korean Medicine, Kyung Hee University, 1Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors: Myoung-Sun
authors: MS
authors: Lee
authors: Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, Seoul, Republic of Korea. strong79@khu.ac.kr.|College of Korean Medicine, Kyung Hee University, 1Hoegi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea. strong79@khu.ac.kr.|Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea. strong79@khu.ac.kr.
authors: Hyo-Jeong
authors: HJ
authors: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053978:Pentacyclic Triterpenes; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D000099157:Sphingosine Kinase
chemical_list: D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053978:Pentacyclic Triterpenes; D017853:Phosphotransferases (Alcohol Group Acceptor); D014315:Triterpenes; D000099157:Sphingosine Kinase; C497442:HIF1A protein, human; C050414:celastrol
keywords: HIF-1α; Hypoxia; Pristimerin; Prostate cancer; SPHK-1