Ki Hyun Yoo

Recombinant canstatin inhibits angiopoietin-1-induced angiogenesis and lymphangiogenesis

We describe the effect of recombinant canstatin, the NC1 domain of the α2 chain of Type IV collagen, on suppression of angiogenesis and lymphangiogenesis both in vitro and in vivo. Recombinant canstatin produced from stably transformed Drosophila S2 cells reduced the expression of angiopoietin‐1 in hypoxia mimetic agent, CoCl2‐treated CT‐26 cells. Recombinant canstatin inhibited proliferation, tube formation and migration of human angiopoietin‐1 (rhAngpt‐1)‐treated human umbilical vein endothelial cells (HUVEC) and lymphatic endothelial cells (LEC). Recombinant canstatin suppressed the expression of Tie‐2 and vascular endothelial growth factor‐3 (VEGFR‐3) transcripts in rhAngpt‐1‐treated HUVEC and LEC, respectively. The inhibitory effect of recombinant canstatin on tumor growth was also investigated using a heterotopic CT‐26 colon carcinoma animal (BALB/c mice) model. Recombinant canstatin reduced the final volume and weight of tumors, and blood and lymphatic vessel densities of tumors, which were evaluated by CD‐31 and LYVE‐1 immunostaining. Immunohistochemical analysis showed that recombinant canstatin dramatically reduced the expression of angiopoietin‐1 in CT‐26 colon carcinoma‐induced tumor, but not the expression of VEGF‐C. Tie‐2 and VEGFR‐3 expressions were also reduced in recombinant canstatin‐treated tumors. These results indicate that recombinant canstatin has anti‐tumoral activities against CT‐26 colon carcinoma cells. Recombinant canstatin reduces the expression of angiopoietin‐1 in hypoxia‐induced CT‐26 cells and inhibits the angiogenic and lymphangiogenic signaling induced by angiopoietin‐1. Recombinant canstatin probably inhibits angiogenesis and lymphangiogenesis via suppression of the integrin‐dependent FAK signaling induced by angiopoietin‐1/Tie‐2 and/or VEGFR‐3.

3‐O‐Acetyloleanolic Acid Induces Apoptosis in Human Colon Carcinoma Hct‐116 Cells

The cytotoxic effect of 3‐O‐acetyloleanolic acid, an oleanolic acid derivative isolated from the seeds of Vigna sinensis K., was investigated in human colon carcinoma HCT‐116 cells. 3‐O‐acetyloleanolic acid dose‐dependently inhibited the viability of HCT‐116 cells. Apoptosis was characterized by detection of cell surface annexin V and sub‐G1 apoptotic cell populations. The number of immunostained cells with annexin V‐FITC was increased after treatment with 3‐O‐acetyloleanolic acid. The sub‐G1 cell population was also increased. Expression of TRAIL‐mediated apoptosis signaling‐related death receptor DR5 was increased in 3‐O‐acetyloleanolic acid‐treated HCT‐116 cells. Activation of caspase‐8 and caspase‐3, critical mediators of extrinsic apoptosis signaling, was also increased by 3‐O‐acetyloleanolic acid. The results indicate that 3‐O‐acetyloleanolic acid induces apoptosis in HCT‐116 cells mediated by an extrinsic apoptosis signaling cascade via up‐regulation of DR5. Copyright

Corosolic Acid Exhibits Anti‐angiogenic and Anti‐lymphangiogenic Effects on In Vitro Endothelial Cells and on an In Vivo CT‐26 Colon Carcinoma Animal Model

We describe the anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid, a pentacyclic triterpenoid isolated from Cornus kousa Burg. A mouse colon carcinoma CT‐26 animal model was employed to determine the in vivo anti‐angiogenic and anti‐lymphangiogenic effects of corosolic acid. Corosolic acid induced apoptosis in CT‐26 cells, mediated by the activation of caspase‐3. In addition, it reduced the final tumor volume and the blood and lymphatic vessel densities of tumors, indicating that it suppresses in vivo angiogenesis and lymphangiogenesis. Corosolic acid inhibited the proliferation and tube formation of human umbilical vein endothelial cells and human dermal lymphatic microvascular endothelial cells. In addition, corosolic acid decreased the proliferation and migration of human umbilical vein endothelial cells stimulated by angiopoietin‐1. Pretreatment with corosolic acid decreased the phosphorylation of focal adhesion kinase (FAK) and ERK1/2, suggesting that corosolic acid contains anti‐angiogenic activity that can suppress FAK signaling induced by angiopoietin‐1. Copyright