Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 12/2010

01.12.2010 | Original Paper

Circulating cycloxygenase-2 in patients with tobacco-related intraoral squamous cell carcinoma and evaluation of its peptide inhibitors as potential antitumor agent

verfasst von: Vaishali Kapoor, Abhay K. Singh, Sharmistha Dey, Suresh C. Sharma, Satya N. Das

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2010

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The aim of this study was to quantitate circulating COX-2 levels in patients with tobacco-related intraoral cancer and to evaluate antitumor activities of COX-2 peptide inhibitors in vitro on KB cell lines.

Patients and methods

We used a novel biosensor-based surface plasmon resonance (SPR) technique for estimation of circulating COX-2 levels in 76 patients with oral cancer and 43 normal individuals. Antitumor activities of five COX-2 inhibitory peptides were evaluated using propidium iodide labeling and flow cytometry, alamar blue, MTS, and annexin-V binding assays.

Results

Patients with oral cancer showed threefold increase in serum COX-2 level when compared to normal controls (P < 0.0001). Further, late-stage tumors and lymph node metastasis were associated with significant increase in serum COX-2 levels. Patients with higher circulating COX-2 also showed higher immunoreactivity to anti-COX-2 antibody in the lesions. The peptides significantly reduced viability and inhibited growth/proliferation, induced cytotoxicity and apoptosis in tumor cells. However, no such effect was observed either on normal human leukocytes or on MCF-7 cell line that did not over express COX-2.

Conclusion

Our results indicate that SPR may be a useful proteomic technique for quantitative assessment of COX-2 and to identify patients with high-risk oral premalignant or occult cancer, as well as in monitoring response to novel COX-2 targeting strategies. Furthermore, COX-2 peptide inhibitors appear to be a new class of potent anticancer agent for human oral carcinoma.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat American Joint Committee on Cancer (1988) Manual for staging of cancer. JB Lippincott, Philadelphia American Joint Committee on Cancer (1988) Manual for staging of cancer. JB Lippincott, Philadelphia
Zurück zum Zitat Bertino JR, Masher MB, Deconti RC (1973) Chemotherapy of cancer of the head and neck. Cancer 31:1141–1149CrossRefPubMed Bertino JR, Masher MB, Deconti RC (1973) Chemotherapy of cancer of the head and neck. Cancer 31:1141–1149CrossRefPubMed
Zurück zum Zitat Castellone MD, Teramoto IT, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a GS- axin-β-catenin signalling axis. Science 310:1504–1510CrossRefPubMed Castellone MD, Teramoto IT, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a GS- axin-β-catenin signalling axis. Science 310:1504–1510CrossRefPubMed
Zurück zum Zitat Cornwall H, Odukoya O, Shklar G (1983) Oral mucosa tumor inhibition by ibuprofen. J Oral Maxillofac Surg 41:795–800CrossRefPubMed Cornwall H, Odukoya O, Shklar G (1983) Oral mucosa tumor inhibition by ibuprofen. J Oral Maxillofac Surg 41:795–800CrossRefPubMed
Zurück zum Zitat Denkert C, Furstenberg A, Daniel PT, Koch I, Köbel M, Weichert W, Siegert A, Hauptmann S (2003) Induction of G o/G 1 cell cycle arrest in ovarian carcinoma cells by the anti inflammatory drug NS-398, but not by COX-2-specific RNA interference. Oncogene 22:8653–8661CrossRefPubMed Denkert C, Furstenberg A, Daniel PT, Koch I, Köbel M, Weichert W, Siegert A, Hauptmann S (2003) Induction of G o/G 1 cell cycle arrest in ovarian carcinoma cells by the anti inflammatory drug NS-398, but not by COX-2-specific RNA interference. Oncogene 22:8653–8661CrossRefPubMed
Zurück zum Zitat El-Hakim IE, Langdon JD (1991) Arachidonic acid cascade and oral squamous cell carcinoma. Clin Otolarygol 16:563–573CrossRef El-Hakim IE, Langdon JD (1991) Arachidonic acid cascade and oral squamous cell carcinoma. Clin Otolarygol 16:563–573CrossRef
Zurück zum Zitat Fields RD, Lancaster MV (1993) Dual attributes continuous monitoring of cell proliferation/cytotoxicity. Am Biotech Lab 11:48–50 Fields RD, Lancaster MV (1993) Dual attributes continuous monitoring of cell proliferation/cytotoxicity. Am Biotech Lab 11:48–50
Zurück zum Zitat GLOBOCAN (2002) Cancer incidence mortality and prevalence world-wide. IARC Press, Lyon GLOBOCAN (2002) Cancer incidence mortality and prevalence world-wide. IARC Press, Lyon
Zurück zum Zitat Grau JJ, Carles J, Monzo M, Palmero R, Artells R, Domingo-Domenech J, Navarro A, Amat M, Fabregat X, Gascon P (2004) Expression of cyclooxygenase-2 mRNA (COX-2-mRNA) in peripheral blood (PB) of head and neck cancer patients (HNC) and healthy controls (HC). Proc J Clin Oncol 22(14S):5521 Grau JJ, Carles J, Monzo M, Palmero R, Artells R, Domingo-Domenech J, Navarro A, Amat M, Fabregat X, Gascon P (2004) Expression of cyclooxygenase-2 mRNA (COX-2-mRNA) in peripheral blood (PB) of head and neck cancer patients (HNC) and healthy controls (HC). Proc J Clin Oncol 22(14S):5521
Zurück zum Zitat Han C, Leng J, Demetris AJ, Wu T (2004) Cycloxygenase-2 promotes human cholangio-carcinoma growth: evidence for cycloxygenase-2—independent mechanism in celecoxib - mediated induction of p21 waf 1/cip1 and p27 kip 1 and cell cycle arrest. Cancer Res 64:1369–1376CrossRefPubMed Han C, Leng J, Demetris AJ, Wu T (2004) Cycloxygenase-2 promotes human cholangio-carcinoma growth: evidence for cycloxygenase-2—independent mechanism in celecoxib - mediated induction of p21 waf 1/cip1 and p27 kip 1 and cell cycle arrest. Cancer Res 64:1369–1376CrossRefPubMed
Zurück zum Zitat Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ (2001) Cycloxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8:97–114CrossRefPubMed Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ (2001) Cycloxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8:97–114CrossRefPubMed
Zurück zum Zitat Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics. CA Cancer J Clin 57(1):43–66CrossRefPubMed Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics. CA Cancer J Clin 57(1):43–66CrossRefPubMed
Zurück zum Zitat Jeng JH, Wang YJ, Chiang BL, Lee PH, Chan CP, Ho YS, Wang TM, Lee JJ, Hahn LJ, Chang MC (2003) Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline. Carcinogenesis 24:1301–1315CrossRefPubMed Jeng JH, Wang YJ, Chiang BL, Lee PH, Chan CP, Ho YS, Wang TM, Lee JJ, Hahn LJ, Chang MC (2003) Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-α production of oral epithelial cells by areca nut extract and arecoline. Carcinogenesis 24:1301–1315CrossRefPubMed
Zurück zum Zitat Khanna NN, Srivastava PK, Khanna S, Das SN (1983) Intensive combination chemo-therapy for cancer of the oral cavity. Cancer 52:790–793CrossRefPubMed Khanna NN, Srivastava PK, Khanna S, Das SN (1983) Intensive combination chemo-therapy for cancer of the oral cavity. Cancer 52:790–793CrossRefPubMed
Zurück zum Zitat Ko SH, Choi GJ, Lee JH, Han YA, Lim SJ, Kim SH (2008) Differential effects of selective cycloxygenase-2 inhibitors in inhibiting proliferation and induction of apoptosis in oral squamous cell carcinoma. Oncol Rep 19:425–433PubMed Ko SH, Choi GJ, Lee JH, Han YA, Lim SJ, Kim SH (2008) Differential effects of selective cycloxygenase-2 inhibitors in inhibiting proliferation and induction of apoptosis in oral squamous cell carcinoma. Oncol Rep 19:425–433PubMed
Zurück zum Zitat Li N, Sood S, Wang S, Fang M, Wang P, Sun Z, Yang CS, Chen X (2005) Over expression of 5-Lipxygenase and Cycloxygenase-2 in Hamster and Human Oral Cancer and chemo-preventive effects of Zileuton and Celecoxib. Clin Cancer Res 11:2089–2096CrossRefPubMed Li N, Sood S, Wang S, Fang M, Wang P, Sun Z, Yang CS, Chen X (2005) Over expression of 5-Lipxygenase and Cycloxygenase-2 in Hamster and Human Oral Cancer and chemo-preventive effects of Zileuton and Celecoxib. Clin Cancer Res 11:2089–2096CrossRefPubMed
Zurück zum Zitat Lim K, Han C, Xu L, Isse K, Demetris AJ, Wu T (2008) Cycloxygenase-2-derived prostaglandin E2 activates β-catenin in human cholangiocarcinoma cells: evidence of inhibition of these signaling pathways by ω3 polyunsaturated fatty acids. Cancer Res 68:553–560CrossRefPubMed Lim K, Han C, Xu L, Isse K, Demetris AJ, Wu T (2008) Cycloxygenase-2-derived prostaglandin E2 activates β-catenin in human cholangiocarcinoma cells: evidence of inhibition of these signaling pathways by ω3 polyunsaturated fatty acids. Cancer Res 68:553–560CrossRefPubMed
Zurück zum Zitat Mackenzie J, Ah-See K, Thakker N, Sloan P, Maran AG, Birch J, Macfarlane GJ (2000) Increasing incidence of oral cancer amongst young persons: what is the etiology? Oral Oncol 36:387–389CrossRefPubMed Mackenzie J, Ah-See K, Thakker N, Sloan P, Maran AG, Birch J, Macfarlane GJ (2000) Increasing incidence of oral cancer amongst young persons: what is the etiology? Oral Oncol 36:387–389CrossRefPubMed
Zurück zum Zitat Marnett LJ, DuBois RN (2002) COX 2: a target for colon cancer prevention. Ann Rev Pharmacol Toxicol 42:55–80CrossRef Marnett LJ, DuBois RN (2002) COX 2: a target for colon cancer prevention. Ann Rev Pharmacol Toxicol 42:55–80CrossRef
Zurück zum Zitat Merrifield RB (1963) The synthesis or a tetrapeptide. J Am Chem Soc 85:2149–2154CrossRef Merrifield RB (1963) The synthesis or a tetrapeptide. J Am Chem Soc 85:2149–2154CrossRef
Zurück zum Zitat Morita I (2002) Distinct function of COX-1 and COX-2. Prostaglandins Other Lipid Mediat 68–69:165–175CrossRefPubMed Morita I (2002) Distinct function of COX-1 and COX-2. Prostaglandins Other Lipid Mediat 68–69:165–175CrossRefPubMed
Zurück zum Zitat Ondrey FG, John SK, Adams GL (1996) Inhibition of head and neck tumor cell growth with arachidonic acid metabolism inhibition. Laryngoscope 106:129–134CrossRefPubMed Ondrey FG, John SK, Adams GL (1996) Inhibition of head and neck tumor cell growth with arachidonic acid metabolism inhibition. Laryngoscope 106:129–134CrossRefPubMed
Zurück zum Zitat Pandey M, Prakash O, Santhi WS, Soumithran CS, Pillai RM (2008) Over expression of COX-2 gene in oral cancer is independent of stage of disease and degree of differentiation. Int J Oral Maxillofac Surg 37:379–383 Pandey M, Prakash O, Santhi WS, Soumithran CS, Pillai RM (2008) Over expression of COX-2 gene in oral cancer is independent of stage of disease and degree of differentiation. Int J Oral Maxillofac Surg 37:379–383
Zurück zum Zitat Papadimitrakopolou VA, William WN Jr, Dannenberg AJ, Lippman SM, Lee JJ, Ondrey FG et al (2008) Pilot randomized phase II study of celecoxib in oral premalignant lesions. Clin Cancer Res 14:2095–2101CrossRef Papadimitrakopolou VA, William WN Jr, Dannenberg AJ, Lippman SM, Lee JJ, Ondrey FG et al (2008) Pilot randomized phase II study of celecoxib in oral premalignant lesions. Clin Cancer Res 14:2095–2101CrossRef
Zurück zum Zitat Perkins TM, Shklar G (1982) Delay in hamster buccal pouch carcinogenesis by aspirin and endomethacin. Oral Surg 53:170–177CrossRefPubMed Perkins TM, Shklar G (1982) Delay in hamster buccal pouch carcinogenesis by aspirin and endomethacin. Oral Surg 53:170–177CrossRefPubMed
Zurück zum Zitat Rigas B, Kashfi K (2005) Cancer prevention: a new era beyond cycloxygenase-2. J Pharmacol Exp Ther 314:1–8CrossRefPubMed Rigas B, Kashfi K (2005) Cancer prevention: a new era beyond cycloxygenase-2. J Pharmacol Exp Ther 314:1–8CrossRefPubMed
Zurück zum Zitat Saba NF, Choi M, Muller S, Shin HJ, Tighiouart M, Papadimitrakopolou VA, El-Naggar AK, Khuri FR, Chen ZG, Shin DM (2009) Role of Cycloxygenase-2 in tumor progression and survival of head and neck squamous cell carcinoma. Cancer Prev Res 2:823–829CrossRef Saba NF, Choi M, Muller S, Shin HJ, Tighiouart M, Papadimitrakopolou VA, El-Naggar AK, Khuri FR, Chen ZG, Shin DM (2009) Role of Cycloxygenase-2 in tumor progression and survival of head and neck squamous cell carcinoma. Cancer Prev Res 2:823–829CrossRef
Zurück zum Zitat Sawhney M, Rohatgi N, Kaur G, Shishodia S, Sethi G, Gupta SD, Deo SVS, Shukla NK, Aggarwal BB, Ralhan R (2007) Expression of NF-κB parallels COX-2 expression in oral pre cancer and cancer: association with smokeless tobacco. Int J Cancer 120:2545–2556CrossRefPubMed Sawhney M, Rohatgi N, Kaur G, Shishodia S, Sethi G, Gupta SD, Deo SVS, Shukla NK, Aggarwal BB, Ralhan R (2007) Expression of NF-κB parallels COX-2 expression in oral pre cancer and cancer: association with smokeless tobacco. Int J Cancer 120:2545–2556CrossRefPubMed
Zurück zum Zitat Shibata M, Kodani I, Osaki M, Araki K, Adachi H, Ryoke K, Ito H (2005) Cycloxygenase-1 and -2 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance. Oral Oncol 41:304–312CrossRefPubMed Shibata M, Kodani I, Osaki M, Araki K, Adachi H, Ryoke K, Ito H (2005) Cycloxygenase-1 and -2 expression in human oral mucosa, dysplasias and squamous cell carcinomas and their pathological significance. Oral Oncol 41:304–312CrossRefPubMed
Zurück zum Zitat Shiotani H, Denda A, Yamamoto K, Kitayama W, Endoh T, Sasaki Y, Tsutsumi N, Sugimura M, Konishi Y (2001) Increased expression of cycloxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide. Cancer Res 61:1451–1456PubMed Shiotani H, Denda A, Yamamoto K, Kitayama W, Endoh T, Sasaki Y, Tsutsumi N, Sugimura M, Konishi Y (2001) Increased expression of cycloxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide. Cancer Res 61:1451–1456PubMed
Zurück zum Zitat Silverman S Jr (2001) Demographic and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge. J Am Dent Assoc 132(Suppl):7S–11SPubMed Silverman S Jr (2001) Demographic and occurrence of oral and pharyngeal cancers. The outcomes, the trends, the challenge. J Am Dent Assoc 132(Suppl):7S–11SPubMed
Zurück zum Zitat Somvanshi RK, Kumar A, Kant S, Gupta D, Singh SB, Das U, Srinivasan A, Singh TP, Dey S (2007) Surface plasmon resonance studies and biochemical evaluation of a potent peptide inhibitor against cycloxygenase-2 as an anti-inflammatory agent. Biochem Biophys Res Commun 361:37–42CrossRefPubMed Somvanshi RK, Kumar A, Kant S, Gupta D, Singh SB, Das U, Srinivasan A, Singh TP, Dey S (2007) Surface plasmon resonance studies and biochemical evaluation of a potent peptide inhibitor against cycloxygenase-2 as an anti-inflammatory agent. Biochem Biophys Res Commun 361:37–42CrossRefPubMed
Zurück zum Zitat Wu T (2005) Cycloxygenase-2 and prostaglandin signaling in cholangiocarcinoma. Biochim Biophys Acta 1755:135–150PubMed Wu T (2005) Cycloxygenase-2 and prostaglandin signaling in cholangiocarcinoma. Biochim Biophys Acta 1755:135–150PubMed
Zurück zum Zitat Wu T, Leng J, Han C, Demetris AJ (2004) The cycloxygenase-2 inhibitor celecoxib blocks phosphorylation of Akt and induces apoptosis in human cholangio-carcinoma cells. Mol Cancer Ther 3:299–307PubMed Wu T, Leng J, Han C, Demetris AJ (2004) The cycloxygenase-2 inhibitor celecoxib blocks phosphorylation of Akt and induces apoptosis in human cholangio-carcinoma cells. Mol Cancer Ther 3:299–307PubMed
Zurück zum Zitat Yang CY, Meng CL, Liao CL, Wong PY (2003) Regulation of cell growth by selective COX-2 inhibitors in oral carcinoma cell lines. Prostaglandins Other Lipid Mediat 72:115–130CrossRefPubMed Yang CY, Meng CL, Liao CL, Wong PY (2003) Regulation of cell growth by selective COX-2 inhibitors in oral carcinoma cell lines. Prostaglandins Other Lipid Mediat 72:115–130CrossRefPubMed
Zurück zum Zitat Zhao X, Goswami M, Pokhriyal N, Ma H, Du H, Yao J, Victor TA, Polyak K, Sturgis CD, Band H, Band V (2008) Cycloxygenase-2 expression during immortalization and breast cancer progression. Cancer Res 68:467–475CrossRefPubMed Zhao X, Goswami M, Pokhriyal N, Ma H, Du H, Yao J, Victor TA, Polyak K, Sturgis CD, Band H, Band V (2008) Cycloxygenase-2 expression during immortalization and breast cancer progression. Cancer Res 68:467–475CrossRefPubMed
Metadaten
Titel
Circulating cycloxygenase-2 in patients with tobacco-related intraoral squamous cell carcinoma and evaluation of its peptide inhibitors as potential antitumor agent
verfasst von
Vaishali Kapoor
Abhay K. Singh
Sharmistha Dey
Suresh C. Sharma
Satya N. Das
Publikationsdatum
01.12.2010
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-010-0837-4

Weitere Artikel der Ausgabe 12/2010

Journal of Cancer Research and Clinical Oncology 12/2010 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.