Effects of the inhibition of cytosolic phospholipase A(2)α in non-small cell lung cancer cells.

Purpose: The aim of this study was to investigate the expression of cPLA(2)α in non-small lung cancer cell lines and tissues, and we sought to determine the in vitro effects of the pyrrolidine-2 inhibitor on cPLA(2)α sensitivity in three different non-small lung cancer cell lines.

Methods: The expression of cPLA(2)α was determined in lung cancer cells by Western blot. Cytotoxicity, cell growth and inhibition of cPLA(2)α activity were determined in relation to the concentration of pyrrolidine-2. Finally, this study investigated immunohistochemical expressions of cPLA(2)α in 23 species of human non-small lung cancer and 5 species of human normal lung to assess their clinicopathological relevance.

Results: cPLA(2)α is expressed in A549 and H460, however, no expression in H661 cells. Pyrrolidine-2 demonstrated a dose-dependent inhibitory effect on cell growth and its significantly inhibited BrdU incorporation of human non-small lung cancer cells. Inhibition with pyrrolidine-2 results in reduction in cPLA(2)α activity in A549 and H460 lung cancer cells by 50% when present at IC(50) concentration in arachidonoyl thio-PC assay. Immunohistochemistry of human lung tissue revealed that cPLA(2)α is increased in lung cancer tissues.

Conclusions: Pyrrolidine-2 is a more potent and specific cPLA(2)α inhibitor than MAFP and AACOCF3 and represents an excellent pharmacological tool to investigate the biosynthesis and the biological roles of cancer. The present study suggests that pyrrolidine-2 could be a potential therapeutic agent for cancer therapy.