Evento
Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice
Ferronato, María Julia
; Salomón, Débora Gisele
; Obiol, Diego Javier
; Alonso, Eliana Noelia
; Fall, Yagamare; Facchinetti, Maria Marta
; Curino, Alejandro Carlos
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Tipo del evento:
Congreso
Nombre del evento:
III Reunión Internacional de Ciencias Farmacéuticas
Fecha del evento:
18/09/2014
Institución Organizadora:
Society of Pharmaceutical Sciences and Research;
Título de la revista:
International Journal of Pharmaceutical Sciences and Research
Editorial:
Society of Pharmaceutical Sciences and Research
ISSN:
2320-5148
e-ISSN:
0975-8232
Idioma:
Inglés
Clasificación temática:
Resumen
1α,25-dihydroxyvitamin D3 (calcitriol) shows potent growth-inhibitory properties on different cancer cell lines although its hypercalcemic effects have severely hampered its therapeutic application. In collaboration with the laboratory of Organic Chemistry of the University of Vigo we synthesized a novel Gemini analogue of calcitriol, called UVB1, in order to maintain or increase the antitumor effects and decrease the calcemic activity. The aim of this study was to evaluate the antitumor action of UVB1 on different tumor cell lines, comparing its effects with those elicited by calcitriol, and studying its calcemic activity and its toxicity in mice. The analog exerts a significant decrease in cell count after treatment with UVB1 in HCT116 (human colorectal cancer), U251 (human glioblastoma), HN13 and HN12 (human head and neck squamous cell carcinoma) and T47D (human breast adenocarcinoma) cell lines. Also, UVB1 reduces cell migration of T98G (human glioblastoma multiforme), HN12 and LM3 (murine mammary adenocarcinoma) cell lines, while cell motility of HC11 (normal murine mammary epithelial cell line) is not affected. Since calcitriol has been shown to generate ROS which is involved in its antiproliferative activity, ROS production was determined in HN13 cell line after treatment with UVB1. An increase in the levels of ROS was observed. Cell cycle analysis by flow cytometry on the same cell line shows that UVB1 induces arrest in the G1/G0 phase and this result is accompanied by a decrease in cyclin D1 levels. The novel analogue, in contrast to calcitriol, did not cause hypercalcemic effects in BALB/c and nude mice. Additionally, histological examination of livers and kidneys showed no pathological changes. Furthermore, animals did not experiment changes in behavior, weight loss or haematocrit alterations. In conclusion, these results suggest that this Gemini analogue may have therapeutic potential as an antitumor drug.
Palabras clave:
ANALOGUE
,
ANTITUMOR-AGENTS
,
CALCITRIOL
,
CANCER
,
CELL-LINES
Archivos asociados
Licencia
Identificadores
Colecciones
Eventos(INIBIBB)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
Novel gemini vitamin D analogue: antitumoral effects on cancer cell lines and lack of calcemic activity in mice; III Reunión Internacional de Ciencias Farmacéuticas; Córdoba; Argentina; 2014; 175-176
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