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

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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.

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Acknowledgments

This study was partly supported by the Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India. VK was recipient of fellowship from DBT.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Tumor Biology and Molecular Immunology Laboratory, Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Vaishali Kapoor & Satya N. Das

  2. Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Abhay K. Singh & Sharmistha Dey

  3. Department of Oto-Rhinolaryngology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Suresh C. Sharma

Authors
  1. Vaishali Kapoor
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  2. Abhay K. Singh
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  5. Satya N. Das
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Corresponding author

Correspondence to Satya N. Das.

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432_2010_837_MOESM1_ESM.tif

Suppl Fig. 1 Immunocytochemical staining of COX-2 in KB and MCF-7 cells (A KB cells negative control treated with secondary antibody only; B KB cells showing intense staining (arrows; original magnification × 10×) C MCF-7 cells negative control treated with secondary antibody only; D MCF-7 tumor cells showing no staining (original magnification × 10×)). (TIFF 1594 kb)

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Kapoor, V., Singh, A.K., Dey, S. et al. Circulating cycloxygenase-2 in patients with tobacco-related intraoral squamous cell carcinoma and evaluation of its peptide inhibitors as potential antitumor agent. J Cancer Res Clin Oncol 136, 1795–1804 (2010). https://doi.org/10.1007/s00432-010-0837-4

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  • DOI: https://doi.org/10.1007/s00432-010-0837-4

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