Although targeting vascular endothelial growth factor-A (VEGF-A) mediated angiogenesis can be an effective therapeutic approach for the treatment of tumors and arthritis, the presently used anti-VEGF-A agents are not only expensive, they also have serious toxicities which preclude their uses in many patients. Therefore many patients have to be taken out of the treatment protocol for these serious side effects thereby, depriving them of the optimal benefits of anti-angiogenic therapy. This necessitates identifying newer inexpensive, non toxic and effective anti-angiogenic molecules which can be safely used in the clinics for the treatment of diseases where angiogenesis plays an important pathogenic role. We here in this study will investigate if chebulinic acid (CI), a tannin commonly and abundantly found in myrobalan fruits can be such an anti- angiogenic agent.
Aim 1 will elucidate the mechanisms by which CI inhibits VEGF-A mediated EC functions.
In Aim 2, the effects of CI on vasculogenesis will be examined. Finally, Aim 3 will determine the efficacy of CI in inhibiting angiogenesis in preclinical tumor and arthritis models because tumor and arthritis are two diseases where the role of VEGF-A mediated neovascularization have been established.
Although anti-angiogenic drugs have shown promise in treatment of several diseases such as tumors and arthritis, but they are very expensive and have serious side effects. Therefore the goal of this proposal is to identify non toxic chebulinic acid, a natural compound abundantly found in myrobalan fruits as an effective anti-angiogenic agent for treatment of several disorders where angiogenesis plays an important role.
| Roy, Soumyabrata; Lu, Kai; Nayak, Mukti Kant et al. (2017) Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells. J Biol Chem 292:435-445 |
