Antiangiogenic Effects of Synthetic Analogs of Curcumin in vivo|
Chandru, H. & Sharada, A.C.
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.
Angiogenesis, Curcumin analogs, BDMP, Neovascularization