Curcumin Analog DM-1 in Monotherapy or Combinatory Treatment with Dacarbazine as a Strategy to Inhibit In Vivo Melanoma Progression

Autor(es)

Faiao-Flores, Fernanda ^[1] ; Quincoces Suarez, Jose Agustin ^[2] ; Fruet, Andrea Costa ^[1] ; Maria-Engler, Silvya Stuchi ^[1] ; Pardi, Paulo Celso ^[3] ; Maria, Durvanei Augusto ^[4]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol, Sao Paulo - Brazil

^[2] Anhanguera Univ Sao Paulo, Organ Synth Lab, UNIAN, Sao Paulo - Brazil

^[3] Anhanguera Univ Sao Paulo, Lab Expt Pathol, UNIAN, Sao Paulo - Brazil

^[4] Butantan Inst, Biochem & Biophys Lab, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 3 MAR 5 2015.
• Citações Web of Science: 14

Resumo

Malignant melanoma is a highly aggressive form of skin cancer with a high mortality rate if not discovered in early stages. Although a limited number of treatment options for melanoma currently exist, patients with a more aggressive form of this cancer frequently decline treatment. DM-1 is a sodium phenolate and curcumin analog with proven anticancer, anti-proliferative and anti-metastatic properties. In this paper, the DM-1 compound showed in vivo antitumor activity alone or in combination with chemotherapeutic DTIC in B16F10 melanoma-bearing mice. Beneficial effects such as melanoma tumor burden reduction with pyknotic nuclei, decreased nuclei/cytoplasmic ratio and nuclear degradation occurred after DM-1 treatment. No toxicological changes were observed in the liver, kidneys, spleen and lungs after DM-1 monotherapy or DTIC combined therapy. DTIC+DM-1 treatment induced the recovery of anemia arising from melanoma and immunomodulation. Both DM-1 treatment alone and in combination with DTIC induced apoptosis with the cleavage of caspase-3, -8 and -9. Furthermore, melanoma tumors treated with DM-1 showed a preferential apoptotic intrinsic pathway by decreasing Bcl-2/Bax ratio. Considering the chemoresistance exhibited by melanoma towards conventional chemotherapy drugs, DM-1 compound in monotherapy or in combination therapy provides a promising improvement in melanoma treatment with a reduction of side effects. (AU)

• Processo FAPESP: 08/56397-8 - Avaliação da atividade antitumoral do composto sintético DM-1 e terapia de captação de nêutrons por boro (BNCT) associados ao quimioterápico dacarbazina no tratamento do melanoma
• Beneficiário: Fernanda Faião Flores
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 11/50435-8 - Síntese de fenóis polifuncionais e seus derivados bioativos
• Beneficiário: José Agustín Pablo Quincoces Suárez
• Linha de fomento: Auxílio à Pesquisa - Regular