Cytotoxic Acting Mechanism Against Tumor Cells Of Jiangxienone From Cordyceps Jiangxiensis

Objective:In an effort to investigate the cytotoxic acting mechanism against tumor cells of of jiangxienone from Cordyceps jiangxiensis.Methods:The cytotoxic effect of jiangxienone against tumor cells was measured by SRB assay, and the efficacy of jiangxienone against huaman gastric cancer cells and against mice bone marrow stromal cells was analyzed by the colony-forming unit-fibroblast (CFU-F) method. Differential expression genes induced by jiangxienone were detected by SSH technology, and gene expression profiling induced by jiangxienone was analyzed using Roche NimbleGen Human Genome Microarray Chip technology in huaman gastric cancer cell. The bioinformatic technique was empolyed to analyze the target genes and/or potential cellular signal pathways, together with fluorescent quantitation real-time PCR technology, gel retardation assay, UV absorption spectrum, and single cell gel electrophoresis methods.Results:The IC50 value of jiangxienone against diffenent huamn gastric cancer cells such as SGC-7901, MGC80-3 and HGC-27 was 1.38μM,2.48μM, and 2.31μM, respectively, and the IC50 vaule of DDP against SGC-7901 tumor cell was 22.04μM. The efficiency ratio of jiangxienone against huaman gastric cancer cells vs mice bone marrow stromal cells was 1.12. Thirty-eight differential expression genes were cloned by SSH, of which 15 genes was associated with cancer disease involving DNA damage and repair, cell cycle, immune and apoptosis.1452 differential expression genes including 621 up-regulation genes and 831 down-regulation genes were identified by microarray technique. Among these genes, there were 61 cancer related-genes,15 of which was involved in DNA damage and repair, the others were associated with cell growth and differentiation, signal transduction, cell cycle, invasion, metastasis, immune, and apoptosis. Further results indicated that jiangxienone could intercalate DNA molecule structure of cancer cells.Conclusion:The molecular mechanism of inhibitory action of jiangxienone on the growth of tumor cells was involved in targeting multiple signaling pathways, and its cytotoxic acting mechanism against tumor cells was associated with DNA damage via intercalating DNA molecular structure.