CALCITRIOL IN COMBINATION WITH DL-BUTHIONINE-S,R-SULFOXIMINE INDUCE ALTERATIONS IN GROWTH, REDOX STATE AND DIFFERENTIATION IN NEOPLASIC INTESTINAL CELLS.

LIAUDAT C.; BOHL L; TOLOSA DE TALAMONI; PICOTTO G

Congreso; XXVIII Reunión Anual Asociación Argentina de Osteología; 2010

CALCITRIOL IN COMBINATION WITH DL-BUTHIONINE-S,R-SULFOXIMINE INDUCE ALTERATIONS IN GROWTH, REDOX STATE AND DIFFERENTIATION IN NEOPLASIC INTESTINAL CELLS. Liaudat AC, Bohl LP, Tolosa de Talamoni NG, Picotto G. Lab. ?Dr. F. Cañas?, Cs. Médicas, UNC, Argentina. Colorectal cancer is considered a multiphasetic process. Colon cancer prognosis and incidence are connected to vitamin D3 serum levels. Non classical actions of 1,25(OH)2D3, the active metabolite of vitamin D3 (calcitriol), have been described. Some of them are growth and adhesion regulation on a variety cell types. Besides, oxidant drugs like D,L-buthionine-S,R-sulfoximine (BSO) increase tumour cell sensibility, specially in resistant cancers. The aim of the study was to evaluate the mechanisms involved in the effects of calcitriol and BSO on colon cancer cell growth. Caco-2 human colon cancer cells were treated with calcitriol (1-200 nM), BSO (2-500 µM), both or vehicle at different times. Cell proliferation was evaluated by crystal violet staining. Catalase (CAT), superoxide dismutase (SOD), alkaline phosphatase (FAL) activities and glutathione levels (GSH) were analysed by spectrophometry. Results were statistically analysed by one way ANOVA and Bonferroni as a test post-hoc. Calcitriol and BSO inhibited Caco-2 growth and this effect was time and dose-depent. Total GSH levels decreased at 6 hs either with BSO or the combined treatment. Calcitriol and calcitriol plus BSO increased FAL levels at 96 hs. CAT activity augmented only with the combinated treatment while SOD activity was not changed by any treatment. In conclusion, BSO increases the antiproliferative effect of calcitriol in Caco-2 cells through oxidative stress induction, which can be only partially compensated by the antioxidant system. FAL increment suggests cell differentiation induction.