TY - JOUR
T1 - Docosahexaenoic Acid Induces Apoptosis in Lung Cancer Cells by Increasing MKP-1
and Down-Regulating p-ERK1/2 and p-p38 Expression.
AU - Serini, Simona
AU - Monego, Giovanni
AU - Calviello, Gabriella
AU - Piccioni, Elisabetta
AU - Boninsegna Lucarelli, Alma
AU - Ranelletti, Franco Oreste
AU - Trombino, Sonia
AU - Oliva, Francesco
AU - Resci, Federica
AU - Picci, Nevio
PY - 2008
Y1 - 2008
N2 - Different agents able to modulate apoptosis have been shown to modify the
expression of the MAP-kinase-phosphatase-1 (MKP-1). The expression of this
phosphatase has been considered a potential positive prognostic factor in lung
cancer, and smoke was shown to reduce the levels of MKP-1 in ferret lung. Our aim
was to assess whether the n-3 polyunsaturated fatty acid docosahexaenoic acid
(DHA), known to inhibit the growth of several cancer cells mainly inducing
apoptosis, may exert pro-apoptotic effect in lung cancer cells by modifying MKP-1
expression. We observed that DHA increased MKP-1 protein and mRNA expression and
induced apoptosis in different lung cancer cell lines (mink Mv1Lu adenocarcinoma
cells, human A549 adenocarcinoma and human BEN squamous carcinoma cells). We
inhibited the pro-apoptotic effect of DHA by treating the cells with the
phosphatase inhibitor Na(3)VO(4) or by silencing the MKP-1 gene with the specific
siRNA. This finding demonstrated that the induction of apoptosis by DHA involved
a phosphatase activity, specifically that of MKP-1. DHA reduced also the levels
of the phosphorylated MAP-kinases, especially ERK1/2 and p38. Such an effect was
not observed when the MKP-1 gene was silenced. Altogether, the data provide
evidence that the DHA-induced overexpression of MKP-1 and the resulting decrease
of MAP-kinase phosphorylation by DHA may underlie the pro-apoptotic effect of
this fatty acid in lung cancer cells. Moreover, they support the hypothesis that
DHA may exert chemopreventive action in lung cancer.
AB - Different agents able to modulate apoptosis have been shown to modify the
expression of the MAP-kinase-phosphatase-1 (MKP-1). The expression of this
phosphatase has been considered a potential positive prognostic factor in lung
cancer, and smoke was shown to reduce the levels of MKP-1 in ferret lung. Our aim
was to assess whether the n-3 polyunsaturated fatty acid docosahexaenoic acid
(DHA), known to inhibit the growth of several cancer cells mainly inducing
apoptosis, may exert pro-apoptotic effect in lung cancer cells by modifying MKP-1
expression. We observed that DHA increased MKP-1 protein and mRNA expression and
induced apoptosis in different lung cancer cell lines (mink Mv1Lu adenocarcinoma
cells, human A549 adenocarcinoma and human BEN squamous carcinoma cells). We
inhibited the pro-apoptotic effect of DHA by treating the cells with the
phosphatase inhibitor Na(3)VO(4) or by silencing the MKP-1 gene with the specific
siRNA. This finding demonstrated that the induction of apoptosis by DHA involved
a phosphatase activity, specifically that of MKP-1. DHA reduced also the levels
of the phosphorylated MAP-kinases, especially ERK1/2 and p38. Such an effect was
not observed when the MKP-1 gene was silenced. Altogether, the data provide
evidence that the DHA-induced overexpression of MKP-1 and the resulting decrease
of MAP-kinase phosphorylation by DHA may underlie the pro-apoptotic effect of
this fatty acid in lung cancer cells. Moreover, they support the hypothesis that
DHA may exert chemopreventive action in lung cancer.
KW - MKP-1
KW - apoptosis
KW - lung cancer cells
KW - n-3 PUFA
KW - MKP-1
KW - apoptosis
KW - lung cancer cells
KW - n-3 PUFA
UR - http://hdl.handle.net/10807/20848
M3 - Article
SP - 1172
EP - 1183
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
SN - 1360-8185
ER -