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

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

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)1795-1804
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume136
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • Anti cancer
  • COX-2
  • Oral cancer
  • Peptide inhibitors
  • Quantitative assessment
  • Spr

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