Inducible Nitric Oxide Synthase-Vascular Endothelial Growth Factor Axis: A Potential Target to Inhibit Tumor Angiogenesis by Dietary Agents

Abstract

Human solid tumors remain latent in the absence of angiogenesis since it is a critical process for their further growth and progression. Experimental evidence suggests that targeting tumor angiogenesis may be a novel strategy to check tumor growth and metastases. Recent studies suggest that several bioactive food components can suppress tumor growth by inhibiting angiogenesis. This suppression occurs because of a direct effect on the tumor, as well as a direct effect on vascular endothelial cells. These food components can target epigenetic processes and thereby suppress the pro-angiogenic tumor microenvironment. One likely epigenetic target is inducible nitric oxide synthase (iNOS). iNOS is known to regulate vascular endothelial growth factor (VEGF) expression, and thereby tumor angiogenesis. The ability of food components to influence the inducible form of cyclooxygenase, COX-2 may also contribute to their impact on tumor growth and angiogenesis. This review focuses on recent developments related to the angiogenic role of the iNOS-VEGF axis and how dietary components may target this axis. Overall, studies suggest that the anti-angiogenic potential of physiologically concentrations of relevant food components could be used as a practical approach for cancer prevention and intervention.

Induction of expression and functional activity of P-glycoprotein efflux transporter by bioactive plant natural products

“…γ-Tocotrienol has been reported to activate the nuclear receptors PXR, which regulates the expression of P-gp encoding gene MDR1 (Zhou et al, 2004). Finally, asiatic acid is a pentacyclic triterpenoid derived from the tropical medicinal plants Centella asiatica and Melaleuca ericifolia (Hsu et al, 2005; Singh and Agarwal, 2007). Several studies have also shown asiatic acid to be cytotoxic in a wide variety of cancer cell lines, including breast cancer, melanoma and myeloma (Hsu et al, 2005), and was reported to have anti-angiogenic and anti-Alzheimer’s activities (Singh and Agarwal, 2007).…”

Inositol Hexaphosphate Inhibits Tumor Growth, Vascularity, and Metabolism in TRAMP Mice: A Multiparametric Magnetic Resonance Study

“…4A). Additional IHC studies were also carried to determine whether IP6 feeding also affects the expression of inducible nitric oxide synthase (iNOS), an enzyme involved in the production of nitric oxide (NO) which facilitates neo-vascularization and invasion (38). The data indicated that IP6 significantly decreases (31–34%, P <0.001 for both doses) iNOS immunoreactivity scores (Fig.…”

Growth factors in the fetus and pre-adolescent offspring of hyperglycemic rats

“…Total ribonucleic acid (RNA) was extracted as previously described. 34 To identify genes that are affected by diabetes with and without insulin treatment, real-time polymerase chain reaction (PCR) was carried out using the rat angiogenesis arrays (Qiagen, USA) using a BioRad IQ5 real-time instrument (BioRad, Hercules, CA) per manufacturer’s instructions.…”

“… 28 – 32 NO modulates insulin sensitivity, 33 and like PGE 2 , interacts with VEGF to promote endothelial cell proliferation, migration, differentiation, and interaction with the extracellular matrix. 34 …”