INVESTIGADORES
MALETTO Belkys AngÉlica
artículos
Título:
Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells.
Autor/es:
LIAUDAT AC, BOHL LP, TOLOSA DE TALAMONI NG, MALETTO B, PISTORESI-PALENCIA MC, PICOTTO G.
Revista:
ANTICANCER DRUGS
Editorial:
LIPPINCOTT WILLIAMS & WILKINS
Referencias:
Lugar: Philadelphia; Año: 2014
ISSN:
0959-4973
Resumen:
The prognosis and incidence of colon cancer are linked
to vitamin D3 serum levels. To evaluate the effects of
D,L-buthionine-S,R-sulfoximine (BSO), 1,25(OH)2D3 and
their combination on intestinal Caco-2 cell growth, to
elucidate the possible cellular mechanisms involved in
their antiproliferative action, and to determine whether
BSO acts as a sensitizer to 1,25(OH)2D3 treatment,
enabling minimization of the toxic effects caused by high
doses of the steroid. Human colon cancer Caco-2 cells
were treated with 1,25(OH)2D3, BSO, both, or vehicle. Cell
proliferation was evaluated by crystal violet staining.
Cell cycle and mitochondrial membrane potential were
measured by flow cytometry. Total glutathione, catalase,
superoxide dismutase, superoxide anion levels, and
alkaline phosphatase activities were analyzed by
spectrophotometry. DNA fragmentation was evaluated
using the terminal dUTP nick end labeling assay. BSO and
1,25(OH)2D3 inhibited Caco-2 cell growth, an effect that
was higher with the combined treatment. The
antiproliferative effect produced by the combination could
be protected by ascorbic acid. BSO plus 1,25(OH)2D3
induced cell cycle arrest and suppressed cell division.
Total glutathione decreased and superoxide anion
increased with BSO and BSO plus 1,25(OH)2D3. Catalase
activity increased with the combined treatment.
Mitochondrial membrane potential and alkaline
phosphatase activity were altered by 1,25(OH)2D3