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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 819, p. 198-206, JAN 15 2018.
• Web of Science Citations: 13

Abstract

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)

• FAPESP's process: 13/01355-7 - In vitro and in vivo study of new compounds: with target-specific (hnRNP K) or action in the mitochondria for use as antitumor oral carcinoma or as cytoprotective in non-tumor cell
• Grantee: Renata Nishida Goto
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer
• Grantee: Carlos Curti
• Support Opportunities: Regular Research Grants