A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity

Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF- and tumor conditioned medium-induced proliferation and ERK signaling of endothelial cells, and VEGF-induced migration and tube formation of endothelial cells. Moreover, MAP2-dRK6 blocks in vivo growth of VEGF-secreting colorectal cancer cells by the suppression of angiogenesis and the subsequent induction of tumor cell apoptosis. Our observations suggest that MAP2-dRK6 can be a prospective therapeutic molecule or lead compound for the development of drugs for various VEGF-related angiogenic diseases.

Effect of mercury ion on the stability of the lipid-protein complex of isolated chloroplasts.

Mercury is known to interact with different parts of living systems causing serious biochemical and physiological disorder. In order to know the effect of mercury (Hg2+) ion on chloroplasts, the cell free organelle are incubated in an isotonic buffer medium in presence of mercury ion. The metal ion is found to induce membrane lipid peroxidation, loss of photosynthetic pigments and degradation of proteins. Such degradation brings about a drastic modification of lipid-protein organization of chloroplasts as reflected from a blue shift of absorption peaks and lowering of chlorophyll-a fluorescence intensity. The detrimental effect of Hg2+ ion has been explained in terms of direct binding with lipid-protein complex of photosynthetic membrane. Such a binding of metal ion exposes the lipid-protein complex for an easier entry and attack of reactive oxygen species (ROS) generated during incubation of chloroplasts in light and dark, thereby resulting in higher disorganization, which is evident from cation- induced changes in absorption and emission characteristics of the organelle.