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

• Published in: Chemico-biological interactions 2022-01, Vol.351, p.109734, Article 109734
• Main Authors: Nascimento, Fernanda Rodrigues, Viktor de Paula Barros Baeta, Jefferson, Prado de França, Andressa Antunes, Braga Rocha e Oliveira, Mariá Aparecida, Pizziolo, Virgínia Ramos, Aparecida dos Santos, Anésia, Antônio de Oliveira Mendes, Tiago, Diaz-Muñoz, Gaspar, Nogueira Diaz, Marisa Alves
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; B16F10; Cell Line, Tumor; Chalcones - chemical synthesis; Chalcones - therapeutic use; DPBP; Male; Melanoma; Melanoma, Experimental - drug therapy; Metastasis; Mice; Mice, Inbred C57BL; Murine model; Oxidative Stress - drug effects
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2021.109734

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 IC50 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. [Display omitted] •1,3-Diphenyl-2-benzyl-1,3-propanedione (DPBP) shows potential as an antitumor agent.•DPBP intercalates into DNA and activates intrinsic and extrinsic apoptotic pathways.•DPBP inhibits tumor growth and angiogenesis in vivo.•Animals treated with DPBP did not show signs of hepatomegaly and nephrotoxicity.•DPBP inhibited metastasis in the model under study.