Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity

Y. Akita, K. Kozaki, T. Nakagawa, S. Saito, [No Value] Ito, S. Tamada, N. Fujiwara, K. Nishikawa, K. Uchida, T. Yoshikawa, O. Noguchi, K. Miyaishi, S. Shimozato, Y. Saga, [No Value] Matsumoto

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: Anti-cancer effects of cyclooxygenase (COX)-2 inhibitors have been reported, but not fully investigated in skin and oral diseases. 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for treating those patients with skin and oral lesions is a highly sophisticated procedure, but the incidence of disease recurrence after treatment is rather significant. Objective: To confirm that COX-2 could be a molecular target in adjunctive therapy to ALA-based PDT, we investigated (i) COX-2 expression in various skin and oral diseases, and (ii) the inhibitory effects on cellular growth of COX-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on human oral squamous cell carcinoma (SCC) cell lines. Methods: A total of 129 biopsy samples from the skin and oral mucosal lesions were tested immunohistochemically for COX-2 expression. Then the in vitro effects of nimesulide, ALA-based PDT, and their combination were determined on two SCC cell lines, HSC-2 and HSC-4. Three different methods (MTT assay, double-staining for annexin V and propidium iodide, caspase-3/CPP32 fluorometric protease assay) were applied for evaluation of their inhibitory effects on these two cell lines. Results: Among the skin diseases, a considerable number of COX-2 high expressers were found in actinic keratosis (15 of 25, 60%), Bowen's disease (13 of 17, 76%) and extramammary Paget's disease (15 of 15, 100%). In contrast, only one of 33 (3%) basal cell carcinoma tumours was a COX-2 high expresser. Among the oral mucosal biopsies, the proportion of COX-2 high expressers increased gradually from hyperplasia (one of six, 17%) through mild dysplasia (five of eight, 63%) and moderate dysplasia (20 of 23, 87%) to severe dysplasia (two of two, 100%). Nimesulide had an inhibitory effect in vitro on HSC-2 (proven to be a COX-2 high expresser), but not on HSC-4 (a COX-2 non-expresser). While ALA-based PDT showed an inhibitory effect on both HSC-2 and HSC-4, most importantly the combination of nimesulide and ALA-based PDT demonstrated a significant synergistic effect on the cellular growth inhibition of only HSC-2, but not of HSC-4. Conclusions: Our study strongly suggests that COX-2 can be one of the molecular targets in treating various skin and oral diseases. The results from our in vitro experiments also prompt us to develop a new protocol with a combination of COX-2 selective inhibitor and ALA-based PDT for more effective treatment of those diseases.

Original languageEnglish
Pages (from-to)472-480
Number of pages9
JournalBritish Journal of Dermatology
Volume151
Issue number2
DOIs
Publication statusPublished - Aug 2004
Externally publishedYes

Fingerprint

Photochemotherapy
Cyclooxygenase 2
Aminolevulinic Acid
nimesulide
Mouth
Skin
Mouth Diseases
Skin Diseases
Cyclooxygenase 2 Inhibitors
Therapeutics
Cell Line
Squamous Cell Carcinoma
Extramammary Paget's Disease
Bowen's Disease
Actinic Keratosis
Biopsy
Propidium
Annexin A5
Basal Cell Carcinoma
Growth

Keywords

  • COX-2 inhibitor
  • Cyclooxygenase-2
  • Oral mucosa
  • Photodynamic therapy
  • Skin

ASJC Scopus subject areas

  • Dermatology

Cite this

Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity. / Akita, Y.; Kozaki, K.; Nakagawa, T.; Saito, S.; Ito, [No Value]; Tamada, S.; Fujiwara, N.; Nishikawa, K.; Uchida, K.; Yoshikawa, T.; Noguchi, O.; Miyaishi, K.; Shimozato, S.; Saga, Y.; Matsumoto, [No Value].

In: British Journal of Dermatology, Vol. 151, No. 2, 08.2004, p. 472-480.

Research output: Contribution to journalArticle

Akita, Y, Kozaki, K, Nakagawa, T, Saito, S, Ito, NV, Tamada, S, Fujiwara, N, Nishikawa, K, Uchida, K, Yoshikawa, T, Noguchi, O, Miyaishi, K, Shimozato, S, Saga, Y & Matsumoto, NV 2004, 'Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity', British Journal of Dermatology, vol. 151, no. 2, pp. 472-480. https://doi.org/10.1111/j.1365-2133.2004.06053.x
Akita, Y. ; Kozaki, K. ; Nakagawa, T. ; Saito, S. ; Ito, [No Value] ; Tamada, S. ; Fujiwara, N. ; Nishikawa, K. ; Uchida, K. ; Yoshikawa, T. ; Noguchi, O. ; Miyaishi, K. ; Shimozato, S. ; Saga, Y. ; Matsumoto, [No Value]. / Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity. In: British Journal of Dermatology. 2004 ; Vol. 151, No. 2. pp. 472-480.
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TY - JOUR

T1 - Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity

AU - Akita, Y.

AU - Kozaki, K.

AU - Nakagawa, T.

AU - Saito, S.

AU - Ito, [No Value]

AU - Tamada, S.

AU - Fujiwara, N.

AU - Nishikawa, K.

AU - Uchida, K.

AU - Yoshikawa, T.

AU - Noguchi, O.

AU - Miyaishi, K.

AU - Shimozato, S.

AU - Saga, Y.

AU - Matsumoto, [No Value]

PY - 2004/8

Y1 - 2004/8

N2 - Background: Anti-cancer effects of cyclooxygenase (COX)-2 inhibitors have been reported, but not fully investigated in skin and oral diseases. 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for treating those patients with skin and oral lesions is a highly sophisticated procedure, but the incidence of disease recurrence after treatment is rather significant. Objective: To confirm that COX-2 could be a molecular target in adjunctive therapy to ALA-based PDT, we investigated (i) COX-2 expression in various skin and oral diseases, and (ii) the inhibitory effects on cellular growth of COX-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on human oral squamous cell carcinoma (SCC) cell lines. Methods: A total of 129 biopsy samples from the skin and oral mucosal lesions were tested immunohistochemically for COX-2 expression. Then the in vitro effects of nimesulide, ALA-based PDT, and their combination were determined on two SCC cell lines, HSC-2 and HSC-4. Three different methods (MTT assay, double-staining for annexin V and propidium iodide, caspase-3/CPP32 fluorometric protease assay) were applied for evaluation of their inhibitory effects on these two cell lines. Results: Among the skin diseases, a considerable number of COX-2 high expressers were found in actinic keratosis (15 of 25, 60%), Bowen's disease (13 of 17, 76%) and extramammary Paget's disease (15 of 15, 100%). In contrast, only one of 33 (3%) basal cell carcinoma tumours was a COX-2 high expresser. Among the oral mucosal biopsies, the proportion of COX-2 high expressers increased gradually from hyperplasia (one of six, 17%) through mild dysplasia (five of eight, 63%) and moderate dysplasia (20 of 23, 87%) to severe dysplasia (two of two, 100%). Nimesulide had an inhibitory effect in vitro on HSC-2 (proven to be a COX-2 high expresser), but not on HSC-4 (a COX-2 non-expresser). While ALA-based PDT showed an inhibitory effect on both HSC-2 and HSC-4, most importantly the combination of nimesulide and ALA-based PDT demonstrated a significant synergistic effect on the cellular growth inhibition of only HSC-2, but not of HSC-4. Conclusions: Our study strongly suggests that COX-2 can be one of the molecular targets in treating various skin and oral diseases. The results from our in vitro experiments also prompt us to develop a new protocol with a combination of COX-2 selective inhibitor and ALA-based PDT for more effective treatment of those diseases.

AB - Background: Anti-cancer effects of cyclooxygenase (COX)-2 inhibitors have been reported, but not fully investigated in skin and oral diseases. 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for treating those patients with skin and oral lesions is a highly sophisticated procedure, but the incidence of disease recurrence after treatment is rather significant. Objective: To confirm that COX-2 could be a molecular target in adjunctive therapy to ALA-based PDT, we investigated (i) COX-2 expression in various skin and oral diseases, and (ii) the inhibitory effects on cellular growth of COX-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on human oral squamous cell carcinoma (SCC) cell lines. Methods: A total of 129 biopsy samples from the skin and oral mucosal lesions were tested immunohistochemically for COX-2 expression. Then the in vitro effects of nimesulide, ALA-based PDT, and their combination were determined on two SCC cell lines, HSC-2 and HSC-4. Three different methods (MTT assay, double-staining for annexin V and propidium iodide, caspase-3/CPP32 fluorometric protease assay) were applied for evaluation of their inhibitory effects on these two cell lines. Results: Among the skin diseases, a considerable number of COX-2 high expressers were found in actinic keratosis (15 of 25, 60%), Bowen's disease (13 of 17, 76%) and extramammary Paget's disease (15 of 15, 100%). In contrast, only one of 33 (3%) basal cell carcinoma tumours was a COX-2 high expresser. Among the oral mucosal biopsies, the proportion of COX-2 high expressers increased gradually from hyperplasia (one of six, 17%) through mild dysplasia (five of eight, 63%) and moderate dysplasia (20 of 23, 87%) to severe dysplasia (two of two, 100%). Nimesulide had an inhibitory effect in vitro on HSC-2 (proven to be a COX-2 high expresser), but not on HSC-4 (a COX-2 non-expresser). While ALA-based PDT showed an inhibitory effect on both HSC-2 and HSC-4, most importantly the combination of nimesulide and ALA-based PDT demonstrated a significant synergistic effect on the cellular growth inhibition of only HSC-2, but not of HSC-4. Conclusions: Our study strongly suggests that COX-2 can be one of the molecular targets in treating various skin and oral diseases. The results from our in vitro experiments also prompt us to develop a new protocol with a combination of COX-2 selective inhibitor and ALA-based PDT for more effective treatment of those diseases.

KW - COX-2 inhibitor

KW - Cyclooxygenase-2

KW - Oral mucosa

KW - Photodynamic therapy

KW - Skin

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