Antiangiogenic Effects of Synthetic Analogs of Curcumin in vivo

The active compound curcumin is isolated from the spice turmeric. Curcumin, curcuminoids and their synthetic analogs have been shown to inhibit the progression of cancer in animal models. In colon and skin carcinogenesis the genetic changes engross different genes, but curcumin is effective in preventing carcinogenesis in both organs. A needful elucidation for this result is that analogues of curcumin can inhibit angiogenesis. The synthetic analog of Curcumin, 1,5 bis (3,5 dimethoxy phenyl) 1,4 pentadiene –3 one (BDMP) was tested for its capacity to inhibit the proliferation of primary endothelial cells in the presence and absence of the basic fibroblast growth factor (bFGF) and its ability to inhibit proliferation of an immortalized endothelial cell line. BDMP and other analogs of curcumin such as bis (3,4 dimethoxyphenyl) 1,3 propanedione (BDMPP), bis (2,4 dimethoxyphenyl) 1,3 propanedione (DMPP), and bis (3,3 dinitrophenyl) 2- bromo 1,3 propanedione (BDNP) were subsequently tested for their ability to inhibit bFGF-induced corneal neovascularization in the mouse cornea. Ultimately, BDMP was evaluated for its ability to inhibit phorbol esterstimulated vascular endothelial growth factor (VEGF) mRNA production. BDMP effectively inhibited endothelial cell proliferation in a dose dependent manner. BDMP, BDMPP, DMPP and BDNP have shown significant inhibition of bFGF mediated corneal neovascularization in the mouse. BDMP had no effect on phorbol ester stimulated VEGF production. Results of these investigations show that BDMP has direct antiangiogenic activity in vitro and in vivo. Carcinogenesis inhibiting activity of the BDMP in skin and colon may be mediated in part through angiogenesis inhibition.