ABSTRACT Cancer is the largest single cause of death in both men and women, claiming over 6 million lives each year world wide. It is well-known that anthracycline derivatives, such as doxorubicin, daurorubicin, and idarubicin have been used extensively in the treatment of certain types of cancers, such as head and neck, breast, gastric, colorectal and lung cancers. Anthraquinone moiety in the structures of anthracyclin play very important role as the mechanism of anticancer agents. Recently, we found that 10-hydroxy-10-C-D-glucosylchrysophanol-9-anthrone (cassialoin) isolated from medicinal plants has potent antitumor and antimetastatic actions, and that the actions of orally administered cassialoin may be due to cassialoin and its metabolites such as chrysophanol-9-anthrone and aloe-emodin through their antiangiogenic activities and/or the modulation of immune systems in the spleen and small intestine in tumor-bearing mice. Furthermore, to search for anticancer agents with stronger activity than resveratrol (3, 4, 5-trihydroxystilbene), we examined the antiangiogenic effects of 21 synthetic and/or natural resveratrol-derived stilbenes. Among these 21 stilbenes, the three dihydroxystilbenes have potent antitumor actions by the inhibition of tumor-induced angiogenesis through the inhibition of vascular endothelial growth factor (VEGF)- induced VEGF receptor (VEGFR)-2 phosphorylation without affecting VEGFR-1 and-2 expression, and VEGF-induced VEGFR-1 phosphorylation in endothelial cells, and pro-matrix metalloproteinase (MMP)-9 expressions in tumor cells.
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