Potentiation of Bleomycin in Jurkat Cells by Fungal Pycnidione

Abstract

Most cancer cells have mutations in genes at the G1 checkpoint and repair DNA only in the G2 phase; therefore, the G2 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 G2 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 G2 phase. Moreover, under these conditions, Chk1 and Chk2 levels were markedly downregulated. Thus, we concluded that pycnidione abrogated bleomycin-induced G2 arrest by decreasing Chk1 and Chk2.

Isomethoxyneihumicin, a new cytotoxic agent produced by marine Nocardiopsis alba KM6-1

“…The cytotoxicities of isomethoxyneihumicin (1 and 2) and 3 against Jurkat cells at 20 h were measured using the MTT assay. 8 Isomethoxyneihumicin and 3 exerted dose-dependent cytotoxic effects with IC 50 values of 6.98 and 30.5 μM, respectively. The cytotoxic effects of isomethoxyneihumicin and 3 on other cancer cells such as HCT116 (human colon carcinoma) cells, HaCaT (human keratinocyte) cells and CHO (Chinese hamster ovary) cells were investigated; however, no cytotoxicity was observed against these cancer cells at 100 μM until 20 h.…”

“…8 In brief, Jurkat cells (5.0 × 10 5 cells in 100 μl) in a 96-well microplate were treated with samples (0-100 μM) at 37°C for 20 h. After being incubated, cells were treated with 10 μl MTT solution (5.5 mg ml − 1 in phosphate-buffered saline), and were then incubated at 37°C for 4 h. A 90-μl aliquot of the lysis solution (40% N, N-dimethylformamide, 2.0% CH 3 COOH, 20% SDS and 0.03 M HCl) was added to each well, and the plates were incubated for 2 h. The absorbance at 550 nm of each well was read with Power Wave 340 (Bio Tek Instruments).…”

Chlokamycin, a New Chloride from the Marine-derived Streptomyces sp. MA2-12

“…Absorbance was read with Power Wave 340 (BIO-TEK INSTRUMENTS INC, Winooski, VT, USA). MTT Analysis: The cytotoxic activities of compounds against Jurkat cells and HCT116 cells were evaluated using the MTT assay, as described previously [7]. In brief, Jurkat cells (5.0 x 10 5 cells in 100 L) in a 96-well microplate were treated with samples (0 to 100 M) at 37°C for 20 h. After being incubated, cells were treated with 10 L MTT solution (5.5 mg mL -1 in phosphate-buffered saline), and were then incubated at 37˚C for 4 h. A 90-L aliquot of lysis solution (40% N, N-dimethylformamide, 2.0% CH 3 COOH, 20% SDS, and 0.03 M HCl) was added to each well, and the plates were incubated for 2 h. The absorbance of each well at 570 nm was read with Power Wave 340.…”

Effect of Bleomycin on Oral Leukoplakia Cell line- an in Vitro Study

“…Bleomycin induces G2/M cell cycle arrest, which is important for genomic stability, in cancer cell lines. It causes senescence, apoptosis and mitotic cell death [18,19,20].…”