Hostname: page-component-7479d7b7d-rvbq7 Total loading time: 0 Render date: 2024-07-11T04:58:46.488Z Has data issue: false hasContentIssue false
  • English
  • Français

Topical chemoprevention of skin cancer in mice, using combined inhibitors of 5-lipoxygenase and cyclo-oxygenase-2

Published online by Cambridge University Press:  08 March 2017

L Fegn  and
Z Wang
L Fegn
Affiliation:
Department of Otolaryngology Head and Neck Surgery, Boston Medical Center, Boston University School of Medicine, Massachusetts, USA Department of Clinical Medicine, Xian Medical Institute, Shanxi, PR China
Z Wang*
Affiliation:
Department of Otolaryngology Head and Neck Surgery, Boston Medical Center, Boston University School of Medicine, Massachusetts, USA
*
Address for correspondence: Dr Zhi Wang, 820 Harrison Ave 4014, Boston, MA 02118, USA. Fax: +1 617 414 1591 E-mail: zwang@bu.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Skin cancer is the most common cancer, and often occurs in the head and neck region. This study aimed to investigate whether a combination of inhibitors of cyclo-oxygenase-2 and 5-lipoxygenase, applied via a microemulsion delivery system, would be effective in topically inhibiting skin carcinogenesis.

Study design:

Randomised animal study.

Methods:

Twenty-four nude mice were intradermally inoculated with carcinoma cells and then divided into three groups (eight animals each): group one received no treatment; group two received celecoxib alone; and group three received a combination of zileuton and celecoxib. Tumour incidence and growth were measured for 14 days.

Results:

Both treatments significantly delayed the onset and development of tumours. However, the combined treatment had the best response (p < 0.01).

Conclusion:

The results clearly showed that topical treatment with either celecoxib alone or celecoxib plus zileuton significantly inhibited skin carcinogenesis, and that a combination of both agents had the best results.

Keywords

Skin NeoplasmsTopical AdministrationChemopreventionInhibitorsMice
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 123 , Issue 8 , August 2009 , pp. 880 - 884
Copyright
Copyright © JLO (1984) Limited 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Presented as a poster at the 14th European Cancer Conference, 23–27 September 2007, Barcelona, Spain.

References

1 Jemal, A, Siegel, R, Ward, E, Murray, T, Xu, J, Thun, MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66CrossRefGoogle Scholar
2 Tsao, AS, Kim, ES, Hong, WK. Chemoprevention of cancer. CA Cancer J Clin 2004;54:150–80CrossRefGoogle ScholarPubMed
3 Wang, W, Polavaram, R, Shapshay, SM. Topical inhibition of oral carcinoma cell with polymer delivered celecoxib. Cancer Lett 2003;198:53–8CrossRefGoogle ScholarPubMed
4 Wilgus, TA, Koki, AT, Zweifel, BS, Rubal, PA, Oberyszyn, TM. Chemotherapeutic efficacy of topical celecoxib in a murine model of ultraviolet light B-induced skin cancer. Mol Carcinog 2003;38:33–9CrossRefGoogle Scholar
5 Wilgus, TA, Breza, TS Jr, Tober, KL, Oberyszyn, TM. Treatment with 5-fluorouracil and celecoxib displays synergistic regression of ultraviolet light B-induced skin tumors. J Invest Dermatol 2004;122:1488–94CrossRefGoogle ScholarPubMed
6 Steele, VE, Holmes, CA, Hawk, ET, Kopelovich, L, Lubet, RA, Crowell, JA et al. Lipoxygenase inhibitors as potential cancer. Chemopreventives. Cancer Epidemiol Biomarkers Prev 1999;8:467–83Google ScholarPubMed
7 Ye, YN, Wu, WK, Shin, VY, Bruce, IC, Wong, BC, Cho, CH. Dual inhibition of 5-LOX and COX-2 suppress colon cancer formation promoted by cigarette smoke. Carcinogenesis 2005;26:827–34CrossRefGoogle ScholarPubMed
8 Li, N, Sood, S, Wang, S, Fang, M, Wang, P, Sunet, Z et al. Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib. Clin Cancer Res 2005;11:2089–96CrossRefGoogle ScholarPubMed
9 Yan, Y, Wang, B, Zuo, YG, Qu, T. Inhibitory effects of mizolastine on ultraviolet B-induced leukotriene B4 production and 5-lipoxygenase expression in normal human dermal fibroblasts in vitro. Photochem Photobiol 2006;82:665–9CrossRefGoogle ScholarPubMed
10 Subramanian, N, Ghosal, SK, Moulik, SP. Topical delivery of celecoxib using microemulsion. Acta Pol Pharm 2004;61:335–41Google ScholarPubMed
11 Shureiqi, I, Lippman, M. Lipoxygenase modulation to reverse carcinogenesis. Cancer Res 2001;61:6307–12Google ScholarPubMed
12 Ara, G, Teicher, BA. Cyclooxygenase and lipoxygenase inhibitors in cancer therapy. Prostaglandins Leukot Essent Fatty Acids 1996;54:3–16CrossRefGoogle ScholarPubMed
13 Wilgus, TA, Koki, AT, Zweifel, BS, Kusewitt, DF, Rubal, PA, Oberyszyn, TM. Inhibition of cutaneous ultraviolet light B-mediated inflammation and tumor formation with topical celecoxib treatment. Mol Carcinog 2003;38:49–58CrossRefGoogle ScholarPubMed
14 Buchanan, FG, Wang, D, Bargiacchi, F, DuBois, RN. Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 2003;278:35451–7CrossRefGoogle ScholarPubMed
15 Pentland, AP, Schoggins, JW, Scott, GA, Khan, KN, Han, R. Reduction of UV induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 1999;20:1939–44CrossRefGoogle ScholarPubMed
16 Hebert, MJ, Takano, T, Holthofer, H, Brady, HR. Sequential morphologic events during apoptosis of human neutrophils. Modulation by lipoxygenase-derived eicosanoids. J Immunol 1996;157:3105–15CrossRefGoogle ScholarPubMed
17 Read, NG, Astbury, PJ, Evans, GO, Goodwin, DA, Rowlands, A. Nephrotic syndrome associated with N-hydroxyureas, inhibitors of 5-lipoxygenase. Arch Toxicol 1995;69:480–90CrossRefGoogle ScholarPubMed
18 Sun, Z, Sood, S, Li, Z, Ramji, D, Yang, P, Newman, RA et al. Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinogenesis by its inhibitors. Carcinogenesis 2006;27:1902–8CrossRefGoogle Scholar
19 Yener, G, Gonullu, U, Uner, M, Degim, T, Araman, A. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of celecoxib through human skin. Pharmazie 2003;58:330–3Google ScholarPubMed
20 Natesan, S, Saroj, SG, Asis, A, Satya, PM. Formulation and physicochemical characterization of microemulsion system using isopropyl myristate, medium-chain glyceride, polysorbate 80 and water. Chem Pharm Bull 2005;53:1530–5Google Scholar