Evidence of Increased Apoptosis and Reduced Proliferation in Basal Cell Carcinomas Treated with Tazarotene Augusto Orlandi, Luca Bianchi, Antonio Costanzo,

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Evidence of Increased Apoptosis and Reduced Proliferation in Basal Cell Carcinomas Treated with Tazarotene Augusto Orlandi, Luca Bianchi, Antonio Costanzo, Elena Campione, Luigi Giusto Spagnoli, Sergio Chimenti Journal of Investigative Dermatology Volume 122, Issue 4, Pages 1037-1041 (April 2004) DOI: 10.1111/j.0022-202X.2004.22414.x Copyright © 2004 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 In vivo and in vitro tazarotene-induced regression: (A) BCC biopsy after 12 wk of topical treatment with 0.1% tazarotene. Basaloid cell aggregates with a small area of central necrosis (white head arrow) and a surrounding moderate dermal lymphoid infiltrate. Immunohistochemical stains showing a small number of Ki-67-positive cells after (B) and increased number of apoptotic cells as demonstrated by TUNEL (C) after 12 wk of treatment with tazarotene. RAR-β (D) and bax protein expression (E) is low or absent in control BCC and increased in tumor biopsies after 12 wk of treatment with tazarotene (F, G). (H) Western blots demonstrate the increase of RAR-β, bax, and caspase-3 cleavage products in C5N but not in B9 cells treated for 48 h with 5μM tazarotene (Taz), whereas RAR-α and -γ, CRBP-1, bcl-2, and control β-actin levels are unchanged. (I) Ladder production after blunt-end linker ligation PCR of 1 μg genomic DNA in B9 and C5N cells. Treatment with 5 μM tazarotene for 48 h increases apoptotic ladder much more in C5N than in B9 cells. MW; φX174 DNA markers from Sigma (D-0672). (J) Concentration-dependent increase of RAR-β in C5N cells cultured for 48 h in the presence of different concentrations of tazarotene (taz). Journal of Investigative Dermatology 2004 122, 1037-1041DOI: (10.1111/j.0022-202X.2004.22414.x) Copyright © 2004 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Effect of tazarotene on growth inhibition and apoptosis: (A) tazarotene-induced growth inhibition in B9 and C5N cultures. At higher concentrations, tazarotene (taz) induces growth inhibition in a greater percentage of C5N than B9 cells (*p=0.05). (B) Pro-apoptotic effect of tazarotene in B9 and C5N cultures. Five μM tazarotene (taz) for 48 h induces a greater percentage of apoptotic cells in C5N cultures (**>p=0.01). Journal of Investigative Dermatology 2004 122, 1037-1041DOI: (10.1111/j.0022-202X.2004.22414.x) Copyright © 2004 The Society for Investigative Dermatology, Inc Terms and Conditions