Boningmycin And Dimethyl Yellow Penicillin Inhibit The Mechanism Of Tumor Cell Proliferation

The anti-tumor antibiotic is the anti-tumor active material which is produced by the microorganism metabolism. There are more than ten kinds of such antibiotics has been applied in clinical, such as Mitomycin, Doxorubicin, bleomycin and so on, which are natural origin anti-tumor antibiotic or Chemical modification similar. And it has become the commonly used medicine in chemotherapy.The present paper studies that Mechanism of cellular senescence induced by boningmycin (BON) and cellular growth-inhibitory effect by Xanthocillin X dimethyl (XXD) in human cancer cells.The cellular senescence is the important step of tumor suppression.The present paper investigated the mechanism of cellular senescence induced by boningmycin in human oral epithelial carcinoma KB cells and non-small cell lung cancer A549 cells,and we has conducted the preliminary study about the mechanism of BON in human breast cancer cells and MCF-7/DOX cells.The anti-tumor medicine can cause the tumour cells to be senescence under the low concentration, which is an important mechanism of the tumor suppression. And in clinical convention, Doxorubicin (DOX), a kind of anti-tumor agent, has been researched often. They found that DOX can induce the most kinds of tumor cells to present the obvious senile characteristic. Therefore, this research uses DOX as a positive comparison medicine.MTT method and clone formation assay were used to detect the growth-inhibitory effect. The results showed that it has the very good growth inhibitory action to the KB cells.Cellular senescence was detected with SA-β-gal staining and discovered that BON can cause the KB cells and A549 cells to be senescence. After KB and A549 cells treated with different concentration BON for 24 h, Cell cycle distribution and accumulation of intracellular reactive oxygen species (ROS) were analyzed with flow cytometry, and Compared with effect of DOX to the cells in the same situation. The results showed that the growth-inhibitory effect of boningmycin was obviously stronger on human oral epithelial carcinoma KB cells than that on non-small cell lung cancer A549 cells. Comparison to the similar action of doxorubicin, boningmycin induced the features of cellular senescence in both cell lines, resulting from arrest at G2/M phase and an increased ROS level. The molecular senescence marker P21 was significantly increased after boningmycin treatment at a dosage of 0.1μmol-L-1, whereas a higher concentration of it induced apoptosis. The results indicated that cellular senescence induced by boningmycin was one of its mechanisms in tumor suppression.BON has the growth inhibitory action to the MCF-7 and MCF-7/DOX cell, resulting from arrest at G2/M phase and activation of apoptosis pathway were detected. its mechanism is related to the induction of apoptosis.One of anti-tumor medicine's effect mechanisms is inducing the tumor cell to apoptosis. The cell apoptosis is the process of programmed cell death which is controlled by gene for maintaining stability of internal environment. It's main morphological characters are, blebbing, chromatin condensation cell shrinkage, nuclear fragmentation,, and chromosomal DNA fragmentation.XXD is secondary metabolite by isolation of aspergillus 3277 fermentation broth. It is architectonic mother nucleus with Xanthocillin. By gyrase B subunit as a target to get drug, it had inhibition activity of Mycobacterium. Considering the similar enzymes in tumor cells, XXD likely also had inhibition of the tumor cells growth.The mechanism of growth-inhibitory effect by Xanthocillin X dimethyl on human oral epithelial carcinoma KB and human hepatoma HepG2 cell was studied.MTT assay was used to detect proliferation-inhibitory effect on the cells; Cell cycle distribution and accumulation of intracellular reactive oxygen species (ROS) were analyzed with flow cytometry. Protein expression was detected by western blotting. Results revealed that the proliferation inhibitory effects of Xanthocillin X dimethyl was obviously on human hepatoma HepG2 cells, human breast cancer MCF-7 cells and human oral epithelial carcinoma KB cells, and the IC50 values were 0.18μg-mL-1,0.38μg-mL-1,0.44μg-mL"1, respectively. Further study found that the arrest at G2/M phase, an increased ROS level and activation of apoptosis pathway were detected after exposure to Xanthocillin X dimethyl. In conclusion, Xanthocillin X dimethyl had obvious inhibition of tumor cell proliferation, and its mechanism is related to the induction of apoptosis.