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  1. Mooi LY, Yew WT, Hsum YW, Soo KK, Hoon LS, Chieng YC
    Asian Pac J Cancer Prev, 2012;13(4):1177-82.
    PMID: 22799301
    Protein kinase C (PKC) has been implicated in carcinogenesis and displays variable expression profiles during cancer progression. Studies of dietary phytochemicals on cancer signalling pathway regulation have been conducted to search for potent signalling regulatory agents. The present study was designed to evaluate any suppressive effect of maslinic acid on PKC expression in human B-lymphoblastoid cells (Raji cells), and to identify the PKC isoforms expressed. Effects of maslinic acid on PKC activity were determined using a PepTag assay for non-radioactive detection of PKC. The highest expression in Raji cells was obtained at 20 nM PMA induced for 6 hours. Suppressive effects of maslinic acid were compared with those of four PKC inhibitors (H- 7, rottlerin, sphingosine, staurosporine) and two triterpenes (oleanolic acid and ursolic acid). The IC₅₀ values achieved for maslinic acid, staurosporine, H-7, sphingosine, rottlerin, ursolic acid and oleanolic acid were 11.52, 0.011, 0.767, 2.45, 5.46, 27.93 and 39.29 μM, respectively. Four PKC isoforms, PKC βI, βII, δ, and ζ, were identified in Raji cells via western blotting. Maslinic acid suppressed the expression of PKC βI, δ, and ζ in a concentration-dependent manner. These preliminary results suggest promising suppressive effects of maslinic acid on PKC activity in Raji cells. Maslinic acid could be a potent cancer chemopreventive agent that may be involved in regulating many downstream signalling pathways that are activated through PKC receptors.
    Matched MeSH terms: Sphingosine/pharmacology
  2. Lee HM, Lo KW, Wei W, Tsao SW, Chung GTY, Ibrahim MH, et al.
    J Pathol, 2017 05;242(1):62-72.
    PMID: 28240350 DOI: 10.1002/path.4879
    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Sphingosine/pharmacology
  3. Omidbakhsh R, Rajabli B, Nasoohi S, Khallaghi B, Mohamed Z, Naidu M, et al.
    Exp Brain Res, 2014 Nov;232(11):3687-96.
    PMID: 25098558 DOI: 10.1007/s00221-014-4052-4
    Lipopolysaccharide is an endotoxin to induce sickness behavior in several animal models to explore the link between immune activation and cognition. Neuroinflammation playing a pivotal role in disease progress is evidently influenced by sphingosine-1-phosphate. As one of the sphingosine analogs in clinical use for multiple sclerosis, fingolimod (FTY720) was shown to substantially affect gene expression profile in the context of AD in our previous experiments. The present study was designed to evaluate the drug efficacy in the context of the mere inflammatory context leading to memory impairment. FTY720 was repeatedly administered for a few days before or after intracerebral lipopolysaccharide (LPS) injection in rats. Animal's brains were then assigned to histological as well as multiplex mRNA assay following memory performance test. Both FTY720 pre-treatment and post-treatment were similarly capable of ameliorating LPS-induced memory impairment as assessed by passive avoidance test. Such amending effects may be partly accountable by the concomitant alterations in transcriptional levels of mitogen-activated protein kinases as well as inflammatory genes determined by QuantiGene Plex analysis. These findings confirming FTY720 application benefits suggest its efficacy may not differ significantly while considered either as a preventive or as a therapeutic approach against neuroinflammation.
    Matched MeSH terms: Sphingosine/pharmacology
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