Mechanism Of Boningmycin On Anti-tumor And Anti-human Papillomavirus

Boningmycin, a new antibiotic of the bleomycin family, is isolated from the-fermentation broth of Streptomycesverticillus var. pingyangensis n.sp. This study aimed to evaluate its antitumor actions and mechanism. The results showed that boningmycin exhibited potent inhibitory effects on several human solid tumor cells and that it was stronger than bleomycin. The administration of boningmycin inhibited the growth of human hepatoma HepG2 xenografts in nude mice, with more efficacy than that of bleomycin. Boningmycin led to an increase of the reactive oxygen species involving iron and caused G2/M phase accumulation in the HepG2 and human breast cancer MCF-7 cells. Two types of cell death, apoptosis and senescence, were detected after exposure to boningmycin. The accumulation of sub-Gl phase cells, an index of apoptosis, and the activation of caspase apoptotic pathways were detected after treatment with higher concentrations of boningmycin. Low concentrations of boningmycin led to a senescent phenotype with an increase in senescence-associatedβ-galactosidase activity and the time-dependent increase of p21, p27, and p53 expressions from 48 to 120 h. Increase of the p21 and p27 expression helps the senescent cells survive in the BON damage. Taken together, the results showed that boningmycin exhibits potent antitumor actions through the induction of apoptosis and cellular.The human papillomavirus (HPV) are small, non-enveloped DNA viruses with a circular genome. Although most papillomavirus infections produce benign lesions, some virus types are associated with the formation of malignant tumours, most notably perhaps cervical cancer. At present, proper cell models and animal models for HPV genetic analyses have severe limitations, so it severely limits genetic analyses of HPVs and for investigating infection processes and validating potential antiviral agents for intervention. Bleomycin has been widely used in the treatment of recalcitrant warts that have failed other types of treatment, but the mechanisms are not very clear. Therefore, this study aimed to evaluate anti-HPV mechanisms of boningmycin. Boningmycin exhibited potent inhibitory effects on HPV positive cells HeLa and that it was stronger than bleomycin and Pingyangmycin. Boningmycin could make infected cells stop proliferation and eventually lead to cell death through the induction of apoptosis and cellular senescence. The accumulation of chromatin condensation, an index of apoptosis, and the activation of caspase apoptotic pathways were detected after treatment with higher concentrations of boningmycin. Low concentrations of boningmycin led to a senescent phenotype with an increase in senescence-associatedβ-galactosidase activity and the time-dependent increase of p21, p27, and p53 expressions. Boningmycin led to an increase of the reactive oxygen species and caused G2/M phase accumulation in the HeLa. Plasmid expressing E2 protein was transiently transfected into HeLa cells along with the E2 responsive reporter described before. The results of this experiment are suggested that boningmycin could repress E2-activated transcription activity. Taken together, the results showed that boningmycin is a promising potential anti-HPV agent for further drug development.