Potentiation of Bleomycin in Jurkat Cells by Fungal Pycnidione

Most cancer cells have mutations in genes at the Cl checkpoint and repair DNA only in the 62 phase; therefore, the 62 checkpoint is a potential target to develop novel therapy. In the course of screening, a known compound, pycnidione, was isolated from the fungal culture broth of Gloeotinia sp. FKI-3416. Pycnidione irreversibly abrogated bleomycin-induced G2 arrest in Jurkat cells and synergically potentiated the cytotoxicity of bleomycin. To elucidate the mechanism of action, the effect of pycnidione on the signal transduction of the 62 checkpoint was analyzed, showing that the increased phospho-cyclin dependent kinase-1 (CDK1) level caused by bleomycin was abrogated in the presence of pycnidione, indicating that cells did not arrest at the 62 phase. Moreover, under these conditions, Chk1 and Chk2 levels were markedly down-regulated. Thus, we concluded that pycnidione abrogated bleomycin-induced 62 arrest by decreasing Chk1 and Chk2.