Anti-cancer activity of a new dihydropyridine derivative, VdiE-2N, in head and neck squamous cell carcinoma

Autor(es):Mostrar menos -

Goto, Renata Nishida ^[1] ; Sobral, Lays Martin ^[1] ; Sousa, Lucas Oliveira ^[1] ; Garcia, Cristiana Bernadelli ^[1] ; Lopes, Norberto Peporine ^[2] ; Marin-Prida, Javier ^[3] ; Ochoa-Rodriguez, Estael ^[4] ; Verdecia-Reyes, Yamila ^[4] ; Lazaro Pardo-Andreu, Gilberto ^[3] ; Curti, Carlos ^[2] ; Leopoldino, Andreia Machado ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP - Brazil

^[3] Univ Havana, Inst Pharm & Food, Ctr Res & Biol Evaluat, Havana - Cuba

^[4] Univ Havana, Fac Chem, Lab Organ Synth, Havana - Cuba

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 819, p. 198-206, JAN 15 2018.
• Citações Web of Science: 13

Resumo

This study aims to examine the effects of a new 1,4-dihydropyridine derivative, VdiE-2N, on cell signaling pathways and mitochondrial events in head and neck squamous cell carcinoma (HNSCC) cells, and on a mice model of xenograft tumor growth/cell proliferation. Four HNSCC cell lines (HN13, HN12, HN6, and CAL27), HEK293 cells (human embryonic kidney 293 cells), and human oral healthy mucosa fibroblasts (OHMF) were used for in vitro assessment of cell viability (resazurin assay) and invasion capacity (modified Boyden chamber assay), and mitochondrial membrane potential (JC-1 fluorescence assay), morphology (transmission electron microscopy), and number of mitochondria (MitoTracker (R) imaging). SET and pDRP1 proteins were analyzed by immunofluorescence, and proteins involved in cell death/survival pathways were analyzed by Western blotting. HN12 xenograft tumors were established in the flank of Balb/c nude mice, and their characteristics and sensitivity to VdiE-2N were determined by immunohistochemistry and histology. VdiE-2N decreased cell viability in HNSCC cells (IC50 = 9.56 and 22.45 mu M for HN13 and HN12 cells, respectively) more strongly than it decreased cell viability in OHMF and HEK293 cells (IC50 = 32.90 and > 50 mu M, respectively). In HN13 cells, VdiE-2N dissipated mitochondrial membrane potential and altered the mitochondria size, shape, and number in a concentration- dependent manner, as well as it induced apoptosis and reduced their invasion capacity. Treatment of mice bearing xenograft tumors with VdiE-2N significantly diminished proliferation of cancer cells. Therefore, VdiE-2N induces HNSCC cell death in vitro through mitochondria-mediated apoptotic pathways and dampens tumor growth in vivo, thus supporting a potential anti-cancer effect. (AU)

• Processo FAPESP: 13/01355-7 - Estudo in vitro e in vivo de novos compostos: com alvo-específico (hnRNP K) ou com ação na mitocôndria para uso como antitumoral em carcinoma oral ou como citoprotetor em célula não-tumoral
• Beneficiário: Renata Nishida Goto
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/10898-4 - Estudo dos mecanismos moleculares associados à proteína SET com impacto na tumorigênese e progressão do câncer oral
• Beneficiário: Carlos Curti
• Modalidade de apoio: Auxílio à Pesquisa - Regular