Docosahexaenoic Acid Induces Apoptosis in Lung Cancer Cells by Increasing MKP-1 and Down-Regulating p-ERK1/2 and p-p38 Expression.

Simona Serini, Sonia Trombino, Francesco Oliva, Elisabetta Piccioni, Giovanni Monego, Federica Resci, Alma Boninsegna Lucarelli, Nevio Picci, Franco Oreste Ranelletti, Gabriella Calviello

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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.
Lingua originaleEnglish
pagine (da-a)1172-1183
Numero di pagine12
Stato di pubblicazionePubblicato - 2008


  • MKP-1
  • apoptosis
  • lung cancer cells
  • n-3 PUFA


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