Anti‐angiogenesis effect of 3′‐sulfoquinovosyl‐1′‐monoacylglycerol via upregulation of thrombospondin 1

Abstract

We previously reported that 3′-sulfoquinovosyl-1′-monoacylglycerol (SQMG) effectively suppresses the growth of solid tumors, likely via its anti-angiogenic activity. To investigate how SQMG affects angiogenesis, we performed DNA microarray analysis and quantitative real-time polymerase chain reaction. Consequently, upregulation of thrombospondin 1 (TSP-1) in SQMG-treated tumors in vitro and in vivo was confirmed. To address the mechanisms of TSP-1 upregulation by SQMG, we established stable TSP-1-knockdown transformants (TSP1-KT) by short hairpin RNA induction and performed reporter assay and in vivo assessment of anti-tumor assay. On the reporter assay, transcriptional upregulation of TSP-1 in TSP1-KT could not be induced by SQMG, thus suggesting that TSP-1 upregulation by SQMG occurred via TSP-1 molecule. In addition, growth of TSP1-KT xenografted tumors in vivo was not inhibited by SQMG, thus suggesting that antiangiogenesis via TSP-1 upregulation induced by SQMG did not occur, as the SQMG target molecule TSP-1 was knocked down in TSP1-KT transformants. These data provide that SQMG is a promising candidate for the treatment of tumor-induced angiogenesis via TSP-1 upregulation. (Cancer Sci 2012; 103: 1546-1552

Anionic glycolipids related to glucuronosyldiacylglycerol inhibit protein kinase Akt

“…Synthesis of monoesters 1a,b 10 Compounds 1a,b were efficiently prepared starting from the known 2-O-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-snglycerol 23a,b (Scheme 1 …”

“…4 Differently from GlcADGs, in the last years both natural and synthetic sulfoquinovosylacylglycerols 25 have been tested for their antitumor, antiviral, anti-inflammatory, immunosuppressive and other bioactivities. [9][10][11][12][13] This prompted us to prepare some SQDG analogues (figure 1) based on 2-O-β-Dglucosylglycerol, which were tested as inhibitors of tumorpromoters in cancer prevention studies. 14a,15 These unnatural 30 sulfolipids, similarly to other glucose-based compounds, 16 display a structure which can be related to that of 3-phosphorylated phosphatidylinositol (PI3P, figure 1), one of the natural phospholipids involved in the regulation of specific lipid-binding domains (e.g.…”

EpsinR, a target for pyrenocine B, role in endogenous MHC‐II‐restricted antigen presentation

“…We applied four sh-RNA technology platforms (Sigma MissionRNAi R , Sigma-Aldrich) to knockdown EpsinR gene expression in BMDCs according to our protocol described previously [31]. Briefly, these sequences were as follows: Esh1; 5 -CCGGGGCAAGGATCAAGGTATAAACCTCGAGGTTTATACCTT GATCCTTGCCTTTTTG-3 , Esh2; 5 -CCGGACGGTGACGACGAAGC ATATCCTCGAGGATATGCTTCGTCGTCACCGTTTTTTG-3 , Esh3; 5 -CCGGCCAATAGAAGTTCGATATATACTCGAGTATATATCGAA CTTCTATTGGTTTTTG-3 , Esh4; 5 -CCGGCCCAGCAGCCATC GCTTAATACTCGAGTATTAAGCGATGGCTGCTGGGTTTTTG-3 , which were cloned into pLKO.1-puro shRNA vector.…”

“…To investigate cell growth or cytotoxicity, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed according to the methods described previously [31]. Briefly, cells (5 × 10 3 cells per well) were cultured in 96-well plates for 24 h, the various amounts of pyrenocine B suspended in PBS were added to the wells, and then cultured.…”

“…The quantitative measurement of gene expression was performed using the LightCycler R system (Roche Applied Science) according to our protocol described previously [31]. Quantitative real-time RT-PCR analyses of mouse glucose-6-phosphate dehydrogenase (G6PDH) and EpsinR gene expression were performed using the LightCycler R FastStart DNA MasterPLUS SYBR Green I system (Roche Applied Science) with the following primer sets: forward primer, 5 -GCACAAGATTGATCGAGA-3 and reverse primer, 5 -GAGGCAGAGTATAGATGGTGTA-3 for the detection of mouse G6PDH; forward primer, 5 -ACAGAATATGCAACAGCCTC-3 and reverse primer, 5 -ACATCCCCATGTTCATGTTC-3 for the detection of mouse EpsinR.…”