One of the most clinically relevant
biological activities of
curcumin is its anti-
cancer property, implicating multiple intracellular pathways in the process. In the present report, we investigated the effect of
curcumin on the activation of apoptotic and anti-angiogenic pathways in
Ehrlich Ascites Tumor (EAT) cells. Treatment with
curcumin in vivo resulted in inhibition of proliferation of EAT cells and
ascites formation. Further, we demonstrate that the induction of apoptosis in EAT cells showed nuclear condensation, DNA fragmentation and translocation of
caspase-activated DNase (CAD) to nucleus upon
curcumin treatment.
Curcumin-induced apoptosis is mediated through activation of
caspase-3, which is specifically inhibited by the
caspase-3 inhibitor,
Ac-DEVD-CHO. On the other hand, the decreased secretion of
ascites by EAT cells is corroborated by reduction in
VEGF secretion upon
curcumin treatment. Further, CD31 immunohistological staining of peritoneum sections in
curcumin-treated mice suggests its efficacy in acting as anti-angiogenic compound in EAT cells by inhibiting proliferation of endothelial cells in mouse peritoneum. However, immunoflurescence studies of
NF-kB revealed that the inhibition of nuclear translocation of
NF-kB p65, a
transcription factor required for
VEGF gene expression, in
curcumin-treated EAT cells. These results suggest a further possible clinical application of this diet-derived compound
curcumin, as both proapoptotic and anti-angiogenic compound in association with conventional chemotherapeutic agents.