Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects
Abstract
:1. Introduction
2. Results
2.1. Bis-(2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) Inhibits the Proliferation of Human Umbilical Vein Endothelial Cells (HUVECs)
2.2. BDDPM Inhibits HUVECs Migration
2.3. BDDPM Inhibits Vessel Sprouting in Vitro
2.4. BDDPM Inhibits Tube Formation on the Matrigel (Growth Factor Enhanced)
2.5. BDDPM Is a Potent Inhibitor of FGFR2, FGFR3, VEGFR2, and PDGFRα
2.6. BDDPM Decreases the Phosphorylation of Akt, Endothelial Nitric Oxide Synthase (eNOS) and Inhibits Endothelial Cell NO Production
3. Discussion
4. Experimental Section
4.1. Materials
4.2. Cell Culture and Proliferation Assay
4.3. Wound Healing Assay
4.4. Spheroid Capillary Sprouting Assay
4.5. Capillary-Like Tube Formation Assay
4.6. In Vitro Kinase Inhibition Assays
4.7. Immunoblotting Analysis
4.8. NO Measurement
4.9. Statistical Analysis
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [PubMed]
- Jain, R.K. Antiangiogenesis strategies revisited: From starving tumors to alleviating hypoxia. Cancer Cell 2014, 26, 605–622. [Google Scholar] [CrossRef] [PubMed]
- Masters, G.A.; Krilov, L.; Bailey, H.H.; Brose, M.S.; Burstein, H.; Diller, L.R.; Dizon, D.S.; Fine, H.A.; Kalemkerian, G.P.; Moasser, M.; et al. Clinical cancer advances 2015: Annual report on progress against cancer from the American Society of Clinical Oncology. J. Clin. Oncol. 2015, 33, 786–809. [Google Scholar] [CrossRef] [PubMed]
- Kurihara, H.; Mitani, T.; Kawabata, J.; Takahashi, K. Two new bromophenols from the red alga Odonthalia corymbifera. J. Nat. Prod. 1999, 62, 882–884. [Google Scholar] [CrossRef] [PubMed]
- Xu, N.; Fan, X.; Yan, X.; Li, X.; Niu, R.; Tseng, C.K. Antibacterial bromophenols from the marine red alga Rhodomela confervoides. Phytochemistry 2003, 62, 1221–1224. [Google Scholar] [CrossRef]
- Oh, K.B.; Lee, J.H.; Chung, S.C.; Shin, J.; Shin, H.J.; Kim, H.K.; Lee, H.S. Antimicrobial activities of the bromophenols from the red alga Odonthalia corymbifera and some synthetic derivatives. Bioorg. Med. Chem. Lett. 2008, 18, 104–108. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Guo, S.J.; Su, H.; Han, L.J.; Shi, D.Y. Total synthesis of bis-(2,3-dibromo-4,5-dihydroxyphenyl)-methane as potent PTP1B inhibitor. Chin. Chem. Lett. 2008, 19, 1290–1292. [Google Scholar] [CrossRef]
- Wu, N.; Luo, J.; Jiang, B.; Wang, L.J.; Wang, S.Y.; Wang, C.H.; Fu, C.Q.; Li, J.; Shi, D.Y. Marine bromophenol bis-(2,3-dibromo-4,5-dihydroxy-phenyl)-methane inhibits the proliferation, migration, and invasion of hepatocellular carcinoma cells via modulating β1-Integrin/Fak signaling. Mar. Drugs 2015, 13, 1010–1025. [Google Scholar] [CrossRef] [PubMed]
- Sakurai, T.; Kudo, M. Signaling pathways governing tumor angiogenesis. Oncology 2011, 81, 24–29. [Google Scholar] [CrossRef] [PubMed]
- Potente, M.; Gerhardt, H.; Carmeliet, P. Basic and therapeutic aspects of angiogenesis. Cell 2011, 146, 873–887. [Google Scholar] [CrossRef] [PubMed]
- Duda, D.G.; Fukumura, D.; Jain, R.K. Role of eNOS in neovascularization: NO for endothelial progenitor cells. Trends Mol. Med. 2004, 10, 143–145. [Google Scholar] [CrossRef] [PubMed]
- Moncada, S. The 1991 Ulf von Euler Lecture. The l-arginine: Nitric oxide pathway. Acta Physiol. Scand. 1992, 145, 201–227. [Google Scholar] [CrossRef] [PubMed]
- Liu, M.; Wang, G.Z.; Xiao, L.; Xu, X.L.; Liu, X.H.; Xu, P.X.; Lin, X.K. Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, a marine algae derived bromophenol, inhibits the growth of Botrytis cinerea and interacts with DNA molecules. Mar. Drugs 2014, 12, 3838–3851. [Google Scholar] [CrossRef] [PubMed]
- Liu, M.; Zhang, W.; Wei, J.T.; Qiu, L.; Lin, X.K. Marine bromophenol bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, induces mitochondrial apoptosis in K562 cells and inhibits topoisomerase I in vitro. Toxicol. Lett. 2012, 211, 126–134. [Google Scholar] [CrossRef] [PubMed]
- Ma, M.; Zhao, J.L.; Wang, S.J.; Li, S.; Yang, Y.C.; Shi, H.G.; Fan, X.; He, L. Bromophenols coupled with methyl γ-ureidobutyrate and bromophenol sulfates from the red alga Rhodomela confervoides. J. Nat. Prod. 2006, 69, 206–210. [Google Scholar] [CrossRef] [PubMed]
- Wang, B.G.; Gloer, J.B.; Ji, N.Y.; Zhao, J.C. Halogenated organic molecules of rhodomelaceae origin: Chemistry and biology. Chem. Rev. 2013, 113, 3632–3685. [Google Scholar] [CrossRef] [PubMed]
- Ferrara, N.; Kerbel, R.S. Angiogenesis as a therapeutic target. Nature 2005, 438, 967–974. [Google Scholar] [CrossRef] [PubMed]
- Gasparini, G.; Longo, R.; Toi, M.; Ferrara, N. Angiogenic inhibitors: A new therapeutic strategy in oncology. Nat. Clin. Pract. Oncol. 2005, 2, 562–577. [Google Scholar] [CrossRef] [PubMed]
- Chung, A.S.; Ferrara, N. Developmental and pathological angiogenesis. Ann. Rev. Cell Dev. Biol. 2011, 27, 563–584. [Google Scholar] [CrossRef] [PubMed]
- Tvorogov, D.; Anisimov, A.; Zheng, W.; Leppanen, V.M.; Tammela, T.; Laurinavicius, S.; Holnthoner, W.; Helotera, H.; Holopainen, T.; Jeltsch, M.; et al. Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. Cancer Cell 2010, 18, 630–640. [Google Scholar] [CrossRef] [PubMed]
- Ebos, J.M.; Kerbel, R.S. Antiangiogenic therapy: Impact on invasion, disease progression, and metastasis. Nat. Rev. Clin. Oncol. 2011, 8, 210–221. [Google Scholar] [CrossRef] [PubMed]
- Bergers, G.; Hanahan, D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 2008, 8, 592–603. [Google Scholar] [CrossRef] [PubMed]
- Lala, P.K.; Orucevic, A. Role of nitric oxide in tumor progression: Lessons from experimental tumors. Cancer Metastasis Rev. 1998, 17, 91–106. [Google Scholar] [CrossRef] [PubMed]
- Cheng, H.; Wang, L.; Mollica, M.; Re, A.T.; Wu, S.; Zuo, L. Nitric oxide in cancer metastasis. Cancer Lett. 2014, 353, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Buttery, L.D.; Springall, D.R.; Andrade, S.P.; Riveros-Moreno, V.; Hart, I.; Piper, P.J.; Polak, J.M. Induction of nitric oxide synthase in the neo-vasculature of experimental tumours in mice. J. Pathol. 1993, 171, 311–319. [Google Scholar] [CrossRef] [PubMed]
- Burke, A.J.; Sullivan, F.J.; Giles, F.J.; Glynn, S.A. The yin and yang of nitric oxide in cancer progression. Carcinogenesis 2013, 34, 503–512. [Google Scholar] [CrossRef] [PubMed]
- Dimmeler, S.; Dernbach, E.; Zeiher, A.M. Phosphorylation of the endothelial nitric oxide synthase at Ser-1177 is required for VEGF-induced endothelial cell migration. FEBS Lett. 2000, 477, 258–262. [Google Scholar] [CrossRef]
- Bono, F.; de Smet, F.; Herbert, C.; de Bock, K.; Georgiadou, M.; Fons, P.; Tjwa, M.; Alcouffe, C.; Ny, A.; Bianciotto, M.; et al. Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties. Cancer Cell 2013, 23, 477–488. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Yoon, Y.C.; Sung, M.J.; Hur, H.J.; Park, J.H. Antiangiogenic properties of cafestol, a coffee diterpene, in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 2012, 421, 567–571. [Google Scholar] [CrossRef] [PubMed]
- Weber, W.; Bertics, P.J.; Gill, G.N. Immunoaffinity purification of the epidermal growth factor receptor. Stoichiometry of binding and kinetics of self-phosphorylation. J. Biol. Chem. 1984, 259, 14631–14636. [Google Scholar] [PubMed]
- Mohammadi, M.; McMahon, G.; Sun, L.; Tang, C.; Hirth, P.; Yeh, B.K.; Hubbard, S.R.; Schlessinger, J. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 1997, 276, 955–960. [Google Scholar] [CrossRef] [PubMed]
- Robertson, S.C.; Meyer, A.N.; Hart, K.C.; Galvin, B.D.; Webster, M.K.; Donoghue, D.J. Activating mutations in the extracellular domain of the fibroblast growth factor receptor 2 function by disruption of the disulfide bond in the third immunoglobulin-like domain. Proc. Natl. Acad. Sci. USA 1998, 95, 4567–4572. [Google Scholar] [CrossRef] [PubMed]
- Hart, K.C.; Robertson, S.C.; Kanemitsu, M.Y.; Meyer, A.N.; Tynan, J.A.; Donoghue, D.J. Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4. Oncogene 2000, 19, 3309–3320. [Google Scholar] [CrossRef] [PubMed]
- Itokawa, T.; Nokihara, H.; Nishioka, Y.; Sone, S.; Iwamoto, Y.; Yamada, Y.; Cherrington, J.; McMahon, G.; Shibuya, M.; Kuwano, M.; et al. Antiangiogenic effect by SU5416 is partly attributable to inhibition of Flt-1 receptor signaling. Mol. Cancer Ther. 2002, 1, 295–302. [Google Scholar] [PubMed]
- Songyang, Z.; Carraway, K.L., 3rd; Eck, M.J.; Harrison, S.C.; Feldman, R.A.; Mohammadi, M.; Schlessinger, J.; Hubbard, S.R.; Smith, D.P.; Eng, C.; et al. Catalytic specificity of protein-tyrosine kinases is critical for selective signalling. Nature 1995, 373, 536–539. [Google Scholar] [CrossRef] [PubMed]
- Baxter, R.M.; Secrist, J.P.; Vaillancourt, R.R.; Kazlauskas, A. Full activation of the platelet-derived growth factor β-receptor kinase involves multiple events. J. Biol. Chem. 1998, 273, 17050–17055. [Google Scholar] [CrossRef] [PubMed]
© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wang, S.; Wang, L.-J.; Jiang, B.; Wu, N.; Li, X.; Liu, S.; Luo, J.; Shi, D. Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects. Int. J. Mol. Sci. 2015, 16, 13548-13560. https://doi.org/10.3390/ijms160613548
Wang S, Wang L-J, Jiang B, Wu N, Li X, Liu S, Luo J, Shi D. Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects. International Journal of Molecular Sciences. 2015; 16(6):13548-13560. https://doi.org/10.3390/ijms160613548
Chicago/Turabian StyleWang, Shuaiyu, Li-Jun Wang, Bo Jiang, Ning Wu, Xiangqian Li, Shaofang Liu, Jiao Luo, and Dayong Shi. 2015. "Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects" International Journal of Molecular Sciences 16, no. 6: 13548-13560. https://doi.org/10.3390/ijms160613548