Lidamycin Cause The Molecular Mechanisms Of Tumor Cell Death

Lidamycin(original name C1027), a member of antitumor antibiotic enediynes, has highly potent cytotoxicities toward tumor cells. It consists of a proprotein and a chromophore, the latter of which has a main actioa It has been observed that lidamycin can directly cleave DNA strands with preference of sequence and nucleotide. In addition to antitumor activities, lidamycin can inhibit the replication of viruses. The accumulating evidences indicate mat lidamycin is a promising drug for clinical usage and valuable to be further studied.In this study, we treated human hepatoma BEL-7402 cells and breast carcinoma MCF-7 cells with lidamycin in order to elucidate the molecular mechanism of its highly potent cytotoxicities toward tumor cells. When the BELr 7402 cells were treated by antitumor agent mitomycin C 30 μ mol/L for 12 h, we observed a typical apoptotic chromatin condensation, that is, detaching from the bottom, rounding, blebbing, using co-staining of fluorescent dyes hoechst 33342 and propidium iodide. However, an normal mode of chromatin condensation occurred when the cells were treated with lidamycin 1 μ mol/L for 6 h, which characterized with adhering on the bottom, chromatin condensing along the nuclear membrane and within the nuclei and no apoptotic bodies. The DNA ladder patterns from the cells treated with lidamycin were observed using agarose gel electrophoresis, and it was detected about 15 min after addition of lidamycin. These phenomena were observed in the MCF-7 cells. Using co-staining of hoechst 33342 and mitochondria-specific fluorecent dye Mitosensor^TM(Clontech), the typical apoptotic cells were green and no appearance of mitochondria when the BEL-7402 cells were treated with mitomycin C; but the cells in treatment with lidamycin for 6 h appeared mitochondria and chromatin condensation. The caspase-3, -6 activities, proteases critical for...