Dibenzoylmethane derivative inhibits melanoma cancer in vitro and in vivo through induction of intrinsic and extrinsic apoptotic pathways.

Autor: Nascimento FR; Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil., Viktor de Paula Barros Baeta J; Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil., Prado de França AA; Department of Biology, Universidade Estadual de Minas Gerais, Ubá, Minas Gerais, 36500-000, Brazil., Braga Rocha E Oliveira MA; Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil., Pizziolo VR; Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil., Aparecida Dos Santos A; Department of General Biology, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil., Antônio de Oliveira Mendes T; Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil., Diaz-Muñoz G; Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil., Nogueira Diaz MA; Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil. Electronic address: marisanogueira@ufv.br.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2022 Jan 05; Vol. 351, pp. 109734. Date of Electronic Publication: 2021 Nov 04.
DOI: 10.1016/j.cbi.2021.109734
Abstrakt: Malignant melanoma has a low incidence, but is the most lethal type of skin cancer. Studies have shown that dibenzoylmethanes (DBMs) have interesting biological activities, including antineoplastic properties. These findings led us to investigate whether news DBM derivatives exert antitumor effects against skin cancers. In a previous study, we found that 1,3-diphenyl-2-benzyl-1,3-propanedione (DPBP) has high in vitro antineoplastic activity against murine B16F10 melanoma cells, with an IC 50 of 6.25 μg/mL. In the current study, we used transdermal and topical formulations of DPBP to evaluate its activity and molecular mechanism of action in a murine model of melanoma. The compound induces tumor cell death with high selectivity (selectivity index of 41.94) by triggering apoptosis through intrinsic and extrinsic pathways. DPBP treatment reduced tumor volume as well as serum VEGF-A and uric acid levels. Hepatomegaly and nephrotoxicity were not observed at the tested doses. Histopathological analysis of sentinel lymph nodes revealed no evidence of metastases. According to the observed data, the DPBP compound was effective for the topical treatment of melanoma cancer, suggesting that it acts as a chemotherapeutic or chemopreventive agent.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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