The effects of Sulindac on cell viability, cell cycle and angiogenesis in pharyngeal cancer cells

Abstract

Objective: The present study aimed to investigate the effects of Sulindac on cell viability, cell cycle and angiogenesis in pharyngeal cancer cell lines (FaDu). Methods: FaDu cells were incubated in a medium in a 5% CO2 incubator at 37°C, after which they were proliferated and passaged. IC50 concentration was used to determine the Sulindac dose. Cells were analyzed for cell viability, cell count and cell cycle after Sulindac administration. Immunohistochemistry (vascular endothelial growth factor receptor 2) and western blot (A disintegrin and metalloproteinase with thrombospondin-like motifs 1-ADAMTS1) analyses were used for angiogenesis assessment. Results: Cell viability decreased in pharyngeal cancer cells after Sulindac administration. In addition, FaDU cells were arrested in the G2/M phase. Sulindac was found to slightly increase vascular endothelial growth factor receptor 2 (VEGF-R2) and decrease ADAMTS1 levels in pharyngeal cancer cells. Conclusion: Sulindac showed positive results on cell proliferation in the treatment of pharyngeal cancer cells. However, it could cause a slight increase in angiogenesis.

Keywords

• Sulindac
• Cell cycle
• Cell viability
• Angiogenesis
• Pharyngeal cancer

Kaynakça

1. 1. Scheper MA, Nikitakis NG, Chaisuparat R, Montaner S, Sauk JJ. Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma. Neoplasia 2007;9:192-9.
2. 2. Forastiere AA, Trotti A, Pfister DG, Grandis JR. Head and neck cancer: recent advances and new standards of care. J Clin Oncol 2006;24:2603-5.
3. 3. Carla C, Daris F, Cecilia B, Francesca B, Francesca C, Paolo F. Angiogenesis in head and neck cancer: a review of the literature. J Oncol 2012;2012:358472.
4. 4. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27.
5. 5. Wang D, Dubois RN. Prostaglandins and cancer. Gut 2006;55:115-22.
6. 6. Mohan S, Epstein JB. Carcinogenesis and cyclooxygenase: the potential role of COX-2 inhibition in upper aerodigestive tract cancer. Oral Oncol 2003;39:537-46.
7. 7. Lin DT, Subbaramaiah K, Shah JP, Dannenberg AJ, Boyle JO. Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. Head Neck 2002;24:792-9.
8. 8. Subbaramaiah K, Dannenberg AJ. Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 2003;24:96-102.

9. 9. Fu SL, Wu YL, Zhang YP, Qiao MM, Chen Y. Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer. World J Gastroenterol 2004;10:1971-4.
10. 10. Thompson HJ, Jiang C, Lu J, et al. Sulfone metabolite of sulindac inhibits mammary carcinogenesis. Cancer Res 1997;57:267-71.
11. 11. Castonguay A, Rioux N. Inhibition of lung tumourigenesis by sulindac: comparison of two experimental protocols. Carcinogenesis 1997;18:491-6.
12. 12. Oida Y, Gopalan B, Miyahara R, et al. Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther 2005;4:291-304.
13. 13. Dvory-Sobol H, Kazanov D, Liberman E, et al. MF tricyclic and sulindac retard tumor formation in an animal model. Int J Cancer 2006;118:11-6.
14. 14. Sun BC, Zhao XL, Zhang SW, Liu YX, Wang L, Wang X. Sulindac induces apoptosis and protects against colon carcinoma in mice. World J Gastroenterol 2005;11:2822-6.
15. 15. Teicher BA, Korbut TT, Menon K, Holden SA, Ara G. Cyclooxygenase and lipoxygenase inhibitors as modulators of cancer therapies. Cancer Chemother Pharmacol 1994;33:515-22.
16. 16. Soriano AF, Helfrich B, Chan DC, Heasley LE, Bunn PA Jr, Chou TC. Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Cancer Res 1999;59:6178-84.
17. 17. Torrance CJ, Jackson PE, Montgomery E, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med 2000;6:1024-8.
18. 18. Yasui H, Adachi M, Imai K. Combination of tumor necrosis factor-alpha with sulindac in human carcinoma cells in vivo. Ann N Y Acad Sci 2003;1010:273-7.
19. 19. Yasui H, Adachi M, Imai K. Combination of tumor necrosis factor-alpha with sulindac augments its apoptotic potential and suppresses tumor growth of human carcinoma cells in nude mice. Cancer 2003;97:1412-20.
20. 20. Ma L, Xie YL, Yu Y, Zhang QN. Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac. World J Gastroenterol 2005;11:1829-32.
21. 21. Choi HJ, Kim HH, Lee HS, et al. Lactacystin augments the sulindac-induced apoptosis in HT-29 cells. Apoptosis 2003;8:301-5.
22. 22. Li X, Gao L, Cui Q, et al. Sulindac inhibits tumor cell invasion by suppressing NF-κB-mediated transcription of microRNAs. Oncogene 2012;31:4979-86.
23. 23. Sauter A, Soulsby H, Hormann K, Naim R. Sulindac sulfone induces a decrease of beta-catenin in HNSCC. Anticancer Res 2010;30:339-43.
24. 24. Thiele W, Sleeman JP. Tumor-induced lymphangiogenesis: a target for cancer therapy? J Biotechnol 2006;124:224-41.
25. 25. Achen MG, Stacker SA. Tumor lymphangiogenesis and metastatic spread-new players begin to emerge. Int J Cancer 2006;119:1755-60.
26. 26. Strauss L, Volland D, Kunkel M, Reichert TE. Dual role of VEGF family members in the pathogenesis of head and neck cancer (HNSCC): possible link between angiogenesis and immune tolerance. Med Sci Monit 2005;11:280-92.
27. 27. Kikuchi K, Kusama K, Sano M, et al. Vascular endothelial growth factor and dendritic cells in human squamous cell carcinoma of the oral cavity. Anticancer Res 2006;26:1833-48.
28. 28. Riedel F, Götte K, Schwalb J, Wirtz H, Bergler W, Hörmann K. Serum levels of vascular endothelial growth factor in patients with head and neck cancer. Eur Arch Otorhinolaryngol 2000;257:332-6.
29. 29. Shemirani B, Crowe DL. Head and neck squamous cell carcinoma lines produce biologically active angiogenic factors. Oral Oncol 2000;36:61-6.
30. 30. Smith BD, Smith GL, Carter D, Sasaki CT, Haffty BG. Prognostic significance of vascular endothelial growth factor protein levels in oral and oropharyngeal squamous cell carcinoma. J Clin Oncol 2000;18:2046-52.
31. 31. Lentsch EJ, Goudy S, Sosnowski J, Major S, Bumpous JM. Microvessel density in head and neck squamous cell carcinoma primary tumors and its correlation with clinical staging parameters. Laryngoscope 2006;116:397-400.
32. 32. Moriyama M, Kumagai S, Kawashiri S, Kojima K, Kakihara K, Yamamoto E. Immunohistochemical study of tumour angiogenesis in oral squamous cell carcinoma. Oral Oncol 1997;33:369-74.
33. 33. Boonkitticharoen V, Kulapaditharom B, Leopairut J, et al. Vascular endothelial growth factor a and proliferation marker in prediction of lymph node metastasis in oral and pharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2008;134:1305-11.
34. 34. Tse GM, Chan AW, Yu KH, et al. Strong immunohistochemical expression of vascular endothelial growth factor predicts overall survival in head and neck squamous cell carcinoma. Ann Surg Oncol 2007;14:3558-65.
35. 35. Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res 2005;11:1434-40.
36. 36. Iruela-Arispe ML, Carpizo D, Luque A. ADAMTS1: a matrix metalloprotease with angioinhibitory properties. Ann N Y Acad Sci 2003;995:183-90.
37. 37. Kuno K, Kanada N, Nakashima E, Fujiki F, Ichimura F, Matsushima K. Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem 1997;272:556-62.
38. 38. Vázquez F, Hastings G, Ortega MA, et al. METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity. J Biol Chem 1999;274:23349-57.
39. 39. Luque A, Carpizo DR, Iruela-Arispe ML. ADAMTS1/METH1 inhibits endothelial cell proliferation by direct binding and sequestration of VEGF165. J Biol Chem 2003;278:23656-65.
40. 40. Lee DW, Sung MW, Park SW, et al. Increased cyclooxygenase-2 expression in human squamous cell carcinomas of the head and neck and inhibition of proliferation by nonsteroidal anti-inflammatory drugs. Anticancer Res 2002;22:2089-96.
41. 41. Rahman MA, Dhar DK, Masunaga R, Yamanoi A, Kohno H, Nagasue N. Sulindac and exisulind exhibit a significant antiproliferative effect and induce apoptosis in human hepatocellular carcinoma cell lines. Cancer Res 2000;60:2085-9.
42. 42. Gallo O, Franchi A, Magnelli L, et al. Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis. Neoplasia 2001;3:53-61.
43. 43. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998;93:705-16.
44. 44. Armutcu F, Demircan K. Emerging roles of ADAMTS metalloproteinases in regenerative medicine and restorative biology. Turk J Biol 2016;40: 308-15.