It has been demonstrated that
nitric oxide (NO) can promote apoptosis in human
cancer cells. To test the protective effects of
antioxidants (
N-acetyl-L-cysteine (LNAC) and
free-radical spin traps (5,5-dimethyl-1-
pyrroline N-
oxide and 2,2,6,6,-tetramethyl-1-piperidinyloxy) against NO-induced apoptosis, a human
colon cancer cell line (COLO 205) was treated with NO, and its survival rate was evaluated both with and without
antioxidant therapy. LNAC arrested the development of progression of apoptosis in COLO 205 cells in a dose-dependent manner, promoted long-term survival, and prevented the internucleosomal DNA cleavage induced by NO. The intracellular level of
glutathione (GSH) was found to be elevated in cells after exposure to LNAC. The
bax protein levels were elevated by NO treatment, and this effect was blocked by LNAC. On the other hand, the bcl-2
oncoprotein level in the LNAC-pretreated cells was significantly elevated in a time-dependent manner compared to cells that received NO pretreatment. In summary, our results suggest that the protective effect of LNAC may be linked to its inducement of increases in cellular GSH and bcl-2
protein levels and to its suppression of cellular
bax protein in treated cells.