Diallyl trisulfide inhibits migration, invasion and angiogenesis of human colon cancer HT-29 cells and umbilical vein endothelial cells, and suppresses murine xenograft tumour growth.
Angiogenesis inhibitors are beneficial for the prevention and treatment of angiogenesis-dependent diseases including cancer. We examined the cytotoxic, anti-metastatic, anti-cancer and anti-angiogenic effects of diallyl trisulfide (DATS). In HT29 cells, DATS inhibited migration and invasion through the inhibition of focal adhesion kinase (FAK), extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 which was associated with inhibition of matrix metalloproteinases-2, -7 and -9 and VEGF. In human umbilical vein endothelial cells (HUVEC), DATS inhibited the migration and angiogenesis through FAK, Src and Ras. DATS also inhibited the secretion of VEGF. The capillary-like tube structure formation and migration by HUVEC was inhibited by DATS. The chicken egg chorioallantoic membrane (CAM) assay indicated that DATS treatment inhibited ex-vivo angiogenesis. We investigated the anti-tumour effects of DATS against human colon cancer xenografts in BALB/c(nu/nu) mice and its anti-angiogenic activity in vivo. In this in-vivo study, DATS also inhibited the tumour growth, tumour weight and angiogenesis (decreased the levels of haemoglobin) in HT29 cells. In conclusion, the present results suggest that the inhibition of angiogenesis may be an important mechanism in colon cancer chemotherapy by DATS.
Department of Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan.
Kuang-Chi
KC
Lai
Shu-Chun
SC
Hsu
Jai-Sing
JS
Yang
Chien-Chih
CC
Yu
Jin-Cherng
JC
Lein
Jing-Gung
JG
Chung
D000498:Allyl Compounds / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019073:HT29 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013440:Sulfides / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000498:Allyl Compounds; D020533:Angiogenesis Inhibitors; D013440:Sulfides; C042577:diallyl trisulfide
DATS; HT-29 human colon adenocarcinoma cells; HUVEC; angiogenesis; migration and invasion