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摘要
We examined the antitumor and antimetastatic actions of 10-hydroxy-anthrone-C-glucoside cassialoin isolated from Cassia garrettiana heartwood in colon 26-bearing mice. Cassialoin (5 and 10 mg/kg) inhibited tumor growth and metastasis to the abdomen and the expression of CD31 (angiogenesis marker) in the tumors, and it increased the numbers of the gamma-interferon (IFN-gamma)-positive, CD8(+) T and natural killer cells in the small intestine or spleen of colon 26-bearing mice. Furthermore, cassialoin inhibited tumor-induced angiogenesis in colon 26-packed chamber-bearing mice. We examined the metabolic activities in the blood, stomach and small intestine after p.o. administration of cassialoin to mice. These results suggest that cassialoin might be converted to chrysophanol through chrysophanol-9-anthrone and metabolized to aloe-emodin from chrysophanol. Chrysophanol-9-anthrone inhibited vascular endothelial growth factor (VEGF) and matrix metallopeptidase-9 expression in colon 26 cells at 5 and 10 mu M, and it inhibited VEGF-induced angiogenesis and migration in human umbilical vein endothelial cells (HUVEC) at 0.5-10 mu M. Furthermore, chrysophanol-9-anthrone inhibited VEGF receptor (VEGFR)-2 expression and VEGF-induced VEGFR-2 phosphorylation. Aloe-emodin also inhibited the VEGF-induced angiogenesis by HUVEC at 1-100 mu M. Cassialoin, chrysophanol-9-anthrone and aloe-emodin enhanced concanavalin A-induced IFN-gamma production in splenocytes of colon 26-bearing mice at a low concentration of 0.1 mu M. From these results, it is suggested that the antitumor and antimetastatic actions of p.o. administered cassialoin may be partly due to cassialoin and its metabolites such as chrysophanol-9-anthrone and aloe-emodin through their anti-angiogenic activities and/or the modulation of the immune systems in the spleen and small intestine in tumor-bearing mice. (Cancer Sci 2008; 99: 2336-2348).
- 出版日期2008-11
