Docosahexaenoic acid (DHA) has been reported to induce tumor cell death by apoptosis. However, little is known about the effects of DHA on autophagy, another complex well-programmed process characterized by the sequestration of cytoplasmic material within autophagosomes. Here, we show that DHA increased both the level of microtubule-associated protein light-chain 3 and the number of autophagic vacuoles without impairing autophagic vesicle turnover, indicating that DHA induces not only apoptosis but also autophagy. We also observed that DHA-induced autophagy was accompanied by p53 loss. Inhibition of p53 increased DHA-induced autophagy and prevention of p53 degradation significantly led to the attenuation of DHA-induced autophagy, suggesting that DHA-induced autophagy is mediated by p53. Further experiments showed that the mechanism of DHA-induced autophagy associated with p53 attenuation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of rapamycin. In addition, compelling evidence for the interplay between autophagy and apoptosis induced by DHA is supported by the findings that autophagy inhibition suppressed apoptosis and further autophagy induction enhanced apoptosis in response to DHA treatment. Overall, our results demonstrate that autophagy contributes to the cytotoxicity of DHA in cancer cells harboring wild-type p53.

Purpose: The purpose of this study was to develop antagonists specific for the vascular endothelial growth factor receptor 1 (VEGFR1) and to investigate the effects of the antagonists on the VEGF-induced endothelial cell functions and tumor progression. Experimental Design: Hexapeptides that inhibit binding of VEGFR1 and VEGF were identified through screening of synthetic peptide library. A selected peptide, anti-Flt1, was investigated for binding specificity with various receptors and ligand peptides. Effects of the peptide on proliferation, cell migration, and fibrin gel^based angiogenesis of endothelial cells were also investigated. The activity of anti-Flt1, in vivo, was evaluated for inhibition of tumor growth and metastasis in VEGF-secreting cancer cell^implanted mice by s.c. injections of the peptide.

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Background: Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues.

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