A preliminary clinical experience suggested tazarotene, a new acetylenic retinoid, as an effective alternative topical treatment of basal cell carcinomas (BCC). The mechanisms of action of this synthetic retinoid, however, have not been yet clarified. In this work we assessed the in vivo effects of daily application of tazarotene for 24 wk, on 30 small superficial and nodular BCC, and the in vitro effects of tazarotene on immortalized basal and squamous tumor epidermal cells. Cellular proliferation, apoptosis and changes in expression of retinol and retinoic acid receptors (RAR), p53, bcl-2, and bax were studied by immunohistochemistry, western blotting and PCR. Overall, 76.7% of treated tumors showed >50% regression. Complete healing was observed in 46.7% of all treated BCC, without recurrences at 2-y observation. Regression was associated with reduced proliferation and increased apoptosis, demonstrated by Ki-67- and TdT-mediated dUTP-biotin nick-end labelling-positive nuclear staining, and with enhanced RAR-beta and bax expression, with RAR-alpha and -gamma expression unchanged. In vitro, tazarotene induced a concentration-dependent increase of RAR-beta and bax associated with a greater rate of apoptosis and growth inhibition in basaloid tumor cells compared with squamous tumor cells. Our studies provide convincing evidence that tazarotene induces BCC regression possibly by synergistic RAR-beta-dependent anti-proliferative and proapoptotic pathways.

Orlandi, A., Bianchi, L., Costanzo, A., Campione, E., Spagnoli, L.g., Chimenti, S. (2004). Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 122(4), 1037-1041 [10.1111/j.0022-202X.2004.22414.x].

Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene

ORLANDI, AUGUSTO;BIANCHI, LUCA;COSTANZO, ANTONIO;Campione, E;SPAGNOLI, LUIGI GIUSTO;CHIMENTI, SERGIO
2004-01-01

Abstract

A preliminary clinical experience suggested tazarotene, a new acetylenic retinoid, as an effective alternative topical treatment of basal cell carcinomas (BCC). The mechanisms of action of this synthetic retinoid, however, have not been yet clarified. In this work we assessed the in vivo effects of daily application of tazarotene for 24 wk, on 30 small superficial and nodular BCC, and the in vitro effects of tazarotene on immortalized basal and squamous tumor epidermal cells. Cellular proliferation, apoptosis and changes in expression of retinol and retinoic acid receptors (RAR), p53, bcl-2, and bax were studied by immunohistochemistry, western blotting and PCR. Overall, 76.7% of treated tumors showed >50% regression. Complete healing was observed in 46.7% of all treated BCC, without recurrences at 2-y observation. Regression was associated with reduced proliferation and increased apoptosis, demonstrated by Ki-67- and TdT-mediated dUTP-biotin nick-end labelling-positive nuclear staining, and with enhanced RAR-beta and bax expression, with RAR-alpha and -gamma expression unchanged. In vitro, tazarotene induced a concentration-dependent increase of RAR-beta and bax associated with a greater rate of apoptosis and growth inhibition in basaloid tumor cells compared with squamous tumor cells. Our studies provide convincing evidence that tazarotene induces BCC regression possibly by synergistic RAR-beta-dependent anti-proliferative and proapoptotic pathways.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/08 - Anatomia Patologica
Settore MED/35 - Malattie Cutanee e Veneree
English
Con Impact Factor ISI
antineoplastic agent; deoxyuridine triphosphate derivative; Ki 67 antigen; protein Bax; protein bcl 2; protein p53; retinoic acid receptor alpha; retinoic acid receptor beta; retinoic acid receptor gamma; retinol; tazarotene; adult; aged; apoptosis; article; basal cell; basal cell carcinoma; cancer recurrence; cancer regression; cell proliferation; clinical article; controlled study; drug effect; drug mechanism; epidermis cell; growth inhibition; healing; human; human cell; immunohistochemistry; in vitro study; in vivo study; nick end labeling; polymerase chain reaction; priority journal; protein expression; skin biopsy; squamous cell carcinoma; Western blotting; aged, 80 and over; bcl-2-associated X Protein; carcinoma basal cell; carcinoma, squamous cell; cell division; cell line, tumor; dermatologic agents; drug administration schedule; middle aged; nicotinic acids; proto-oncogene proteins; proto-oncogene proteins c-bcl-2; receptors, retinoic acid; skin neoplasms; treatment outcome
Orlandi, A., Bianchi, L., Costanzo, A., Campione, E., Spagnoli, L.g., Chimenti, S. (2004). Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 122(4), 1037-1041 [10.1111/j.0022-202X.2004.22414.x].
Orlandi, A; Bianchi, L; Costanzo, A; Campione, E; Spagnoli, Lg; Chimenti, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/31243
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