A JNK inhibitor SP600125 induces defective cytokinesis and enlargement in P19 embryonal carcinoma cells.

While analyzing the role of c-Jun NH(2)-terminal kinase (JNK) in neurogenesis in P19 embryonal carcinoma cells, we noticed that treatment with SP600125, a JNK inhibitor, increased the cell size markedly. SP600125-induced enlargement of P19 cells was time- and dose-dependent. The increased cell size in response to SP600125 was also detected in B6mt-1 embryonic stem cells. SP600125 treatment inhibited cell growth and increased DNA contents, indicating the inhibition of cell proliferation resulting from endoreduplication. Concurrently, the gene expression of p21, a regulator of G2/M arrest as well as G1 arrest, was increased in cells treated with SP600125. The increased cell size in response to SP600125 was detected even in P19 cells treated with colcemide, an inhibitor of cell cycle progression at the metaphase. The present study suggests that treatment with SP600125 progresses the cell cycle, skipping cytokinesis in P19 cells.