Role of active components of curcumin in anti-angiogenesis in vitro

Objective To explore the anti-angiogenesis effects of active components (curcumin-1, curcumin-2 and curcumin-3) of Curcuma Longa. Methods ①Human umbilical vein endothelial cell lines (HUVEC) and human pulmonary microvascular endothelial cell lines(HPMEC) were employed to analyze and compare the inhibitory effects on cell proliferation and apoptosis of the active components. ②Nude mice bearing with human lung adenocarcinoma cell line A549 were injected intraperitoneally with purified curcumin-3 to observe the inhibitory effects on angiogenesis. Results ①The IC 50 values of inhibitory effect of curcumin-1, curcumin-2 and curcumin-3 on HUVEC growth were 0.525 μg/ml, 0.399 μg/ml and 0.125 μg/ml, respectively. At the concentration of 4 μg/ml, curcumin-1, curcumin-2 and curcumin-3 were able to inhibit effectively the proliferation of endothelial cell at 48 h post-treatment (P0.05), and reached the peak at 72 h post-treatment. ②At the concentration of 4 μg/ml, curcumin-3 could effectively retard the endothelial cell at S phase at 24 h post-treatment (P0.05). But when the concentration was 8 μg/ml or more, curcumin-3 could also induce obvious apoptosis of endothelial cell. ③MVD (micro vein density) in curcumin-3 group was lower than that in control group, respectively (P0 01). Curcumin-3 markedly suppressed the expression of vascular endothelium growth factor (VEGF) and its receptors, Flt-1 and KDR in xenografted tumor tissues, as compared with the control group (P0.01). Conclusion Curcumin-1, curcumin-2 and curcumin-3 can significantly inhibit angiogenesis in cultured human endothelial cells and tumor tissues in nude mice bearing with human lung adenocarcinoma cell line A549. The bioactivity of curcumin-3 is significantly higher than that of curcumin-1 and curcumin-2, respectively. The possible mechanisms involved in the suppression of angiogenesis may be related to down-regulation of VEGF, Flt-1and KDR in tumor cells and endothelial cells.