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Preparing a 68Ga-labeled Arginine Glycine Aspartate RGD-peptide for Angiogenesis
Published on: January 7, 2019
14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis
Jaeok Lee1, Pavitra Kumar2, Suganya Natarajan2
1Pharmaceutical Laboratory, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Abstract:
Over the past few decades, VEGF-targeted antiangiogenic therapy for cancers has gained increasing attention. Nevertheless, there are still several limitations such as the potential resistance mechanisms arising in cancer cells against these therapies and their potential adverse effects. These limitations highlight the need for novel anti-angiogenesis molecules and better understanding of the mechanisms of tumor angiogenesis. In the present study, we investigated the antiangiogenic properties of a novel 14-mer antiangiogenic peptide (14-MAP) derived from N-terminal 14 kDa buffalo prolactin and characterized its mode of action. 14-MAP at the picomolar concentration inhibited VEGF- and bradykinin (an autacoid peptide expressed in vascular tissues in pathophysiology, BK)-stimulated endothelial nitric oxide (eNO) production, cell migration, and proliferation in endothelial cells and vessel development in the chick embryo. Although this peptide inhibited both VEGF- and BK-dependent angiogenic processes, its action was more pronounced in the latter. Moreover, the interference of 14-MAP with the eNO synthase (eNOS)-cyclic GMP pathway was also identified. A combination of a low dose of Avastin, a widely used drug targeting VEGF-dependent angiogenesis, and 14-MAP significantly reduced tumor size in an in vivo model of human colon cancer. Taken together, our results suggest that 14-MAP, a BK- and eNOS-dependent antiangiogenic peptide, might be useful for overcoming the limitation of VEGF-targeted antiangiogenic therapy in cancer patients. However, further studies will be required to further characterize its mode of action and therapeutic potential.
Insights
A novel peptide, 14-MAP, shows anti-angiogenic properties by inhibiting endothelial nitric oxide production. This peptide may overcome limitations in current VEGF-targeted cancer therapies.
Area of Science:
- Oncology
- Vascular Biology
- Biochemistry
Background:
- VEGF-targeted antiangiogenic therapy is crucial for cancer treatment but faces limitations like resistance and adverse effects.
- Novel anti-angiogenesis molecules and a deeper understanding of tumor angiogenesis mechanisms are needed.
- Buffalo prolactin's N-terminal 14 kDa fragment yields a novel 14-mer antiangiogenic peptide (14-MAP).
Purpose of the Study:
- To investigate the anti-angiogenic properties of the novel 14-mer antiangiogenic peptide (14-MAP).
- To characterize the mode of action of 14-MAP in endothelial cells and tumor angiogenesis.
- To evaluate the therapeutic potential of 14-MAP in combination with existing anti-angiogenic drugs.
Main Methods:
- Assessed 14-MAP's effect on endothelial nitric oxide (eNO) production, cell migration, and proliferation stimulated by VEGF and bradykinin (BK).
- Evaluated 14-MAP's impact on vessel development in chick embryos.
- Investigated 14-MAP's interference with the eNOS-cyclic GMP pathway.
- Tested a combination therapy of 14-MAP and Avastin in a human colon cancer xenograft model.
Main Results:
- 14-MAP inhibited VEGF- and BK-stimulated eNO production, endothelial cell migration, and proliferation at picomolar concentrations.
- The peptide demonstrated significant inhibition of endothelial cell functions and vessel development.
- 14-MAP interfered with the eNOS-cyclic GMP pathway, with a more pronounced effect on BK-dependent processes.
- Combination therapy with Avastin significantly reduced tumor size in vivo.
Conclusions:
- 14-MAP exhibits potent anti-angiogenic activity, acting via BK and eNOS pathways.
- This peptide shows promise in overcoming limitations associated with current VEGF-targeted therapies.
- Further research is warranted to fully elucidate 14-MAP's mechanism of action and therapeutic efficacy.
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