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 anti-angiogenesis 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.

• Authors: Kayo Matsuki, Atsushi Tanabe, Ayumi Hongo, Fumio Sugawara, Kengo Sakaguchi, Nobuaki Takahashi, Noriyuki Sato, Hiroeki Sahara
• Journal: Cancer science (Cancer Sci) Vol. 103 Issue 8 Pg. 1546-52 (Aug 2012) ISSN: 1349-7006 [Electronic] England
• PMID: 22587436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Japanese Cancer Association.

Chemical References

• 3'-sulfonoquinovosyl-1'-monoacylglyceride
• Angiogenesis Inhibitors
• Glycolipids
• Monoglycerides
• Thrombospondin 1

Topics

• Adenocarcinoma (genetics, metabolism)
• Angiogenesis Inhibitors (genetics, pharmacology)
• Animals
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Gene Expression Profiling
• Glycolipids (pharmacology)
• Immunohistochemistry
• Mice
• Monoglycerides (pharmacology)
• Oligonucleotide Array Sequence Analysis
• Real-Time Polymerase Chain Reaction
• Thrombospondin 1 (genetics, metabolism)
• Transcriptome
• Up-Regulation (drug effects)