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

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Orlandi A, Bianchi L, Costanzo A, Campione E, Giusto Spagnoli L, Chimenti S

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

J Invest Dermatol. 2004 Apr;122(4):1037-41.

PubMed ID

15102095 [ View in PubMed

]

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 pro-apoptotic pathways.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tazarotene	Retinoic acid receptor beta	Protein	Humans	Yes	Agonist	Details