AIM: The compound B19(C21 H22 O5) is a newly synthesized, mono-carbonyl analog of curcumin that has exhibited potentialantitumor effects. This present study was performed to identify the anti-angiogenic activity of this compound. METHODS AND RESULTS: B19 inhibited migration and tube formation of human umbilical vein endothelial cells, and arrested microvessel outgrowth from rat aortic rings.In addition, B19 suppressed the neovascularization of chicken chorioallantoic membrane. Mechanistic studies revealed that B19 suppressed the downstream protein kinase activation of vascular endothelial growth factor(VEGF) by decreasing phosphorylated forms of serine/threonine kinase Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase, with or without stimulating vascular endothelial growth factor(VEGF). CONCLUSIONS: B19 exerted anti-angiogenic activity in vitro and ex vivo, which suggests that it merits further investigation as a promising anticancer angiogenesis compound.
SUN LiLIU JinLIN Sen-SenSHI Wen-TingZHU JingLIANG GuangYUAN Sheng-Tao
AIM: To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action. METHODS: MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogon japonicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor(VEGF), C-C chemokine receptor type 5(CCR5) and hypoxia-inducible factor 1α(HIF-1α) were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay. RESULTS: At 0.01 to 1 μmol?L-1, DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1α. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo. CONCLUSION: DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-1α expression.
AIM: To investigate the effect of DT-13 on gastric cancer cell migration, and to explore the possible mechanisms underlying the anti-metastasis activity of DT-13. METHODS: Growth inhibition of DT-13 was analyzed by the MTT assay. Cell migration was measured by the scratch-wound assay and transwell double chamber assay. To investigate the possible mechanisms underlying the anti-metastasis activity of DT-13, chemokine receptors that are involved in cancer metastasis(CCR2, CCR5, CCR7, CXCR4, and CXCR6) were detected by conventional PCR. The effect of DT-13 on CCR5 and CXCR4 expression was further evaluated by quantitative PCR and Western blot, respectively. The secretion of CCL5(ligand of CCR5) and SDF-1(ligand of CXCR4) were detected by enzyme-linked immunosorbent assay(ELISA). RESULTS: DT-13 inhibited BGC-823 and HGC-27 cell growth in a dose dependent manner, and the estimated IC50 value for 24 h treatment was 23.5 ± 5.1 μmol·L-1 for BGC-823 cells and 35.6 ± 7.6 μmol·L-1 for HGC-27 cells. DT-13 also significantly decreased gastric cancer cell migration. DT-13 significantly decreased the gene expression of CCR5 in both BGC-823 and HGC-27 gastric cancer cells, and moderately reduced the expression of CXCR4. Similar to the results of gene expression, significant down-regulation of CCR5 protein was observed, but CXCR4 protein levels were much less affected. CCL5 secretion, but not SDF-1 production, was inhibited by DT-13. CONCLUSION: DT-13 inhibited gastric cancer cell migration by down-regulation of the CCR5-CCL5 axis.
LIN Sen-SenFAN WeiSUN LiLI Fang-FangZHAO Ren-PingZHANG Lu-YongYU Bo-YangYUAN Sheng-Tao
