title: BF-30 selectively inhibits melanoma cell proliferation via cytoplasmic membrane permeabilization and DNA-binding in vitro and in B16F10-bearing mice.
abstract: Cathelicidin-BF (BF-30) is a cathelicidin-like polypeptide composed of 30 amino acids and is a natural antibacterial peptide extracted from the venom of the snake Bungarus fasciatus. In our previous study, BF-30 showed broad antimicrobial activity against drug-resistant bacteria through enhancing the cytoplasmic membrane permeability. However, the anticancer activity of BF-30 has not yet been investigated. In this study, the effects of BF-30 on the proliferation of the metastatic melanoma cell line B16F10 in vitro and in vivo, as well as the mechanism were studied. Assay of cell viability, a B16F10-bearing mouse model, and histochemical examination were utilized to investigate the anti-tumor effects of BF-30. In addition, transmission electron microscope analysis, lactate dehydrogenase release assay, DNA retardation assay, Real-time PCR, Western blot, wound healing assay, and chick embryo chorioallantoic membrane assay were applied to elucidate the mechanism of BF-30 on B16F10. BF-30 inhibited B16F10 and B16 proliferation in vitro in a dose- and time-dependent manner with an IC50 of 7.3 µM and 13.9 µM, respectively. Moreover, BF-30 significantly suppressed melanoma growth in B16F10-bearing mice without body weight loss. The observed inhibition were 41.4%, 49.5% and 63.5% at the doses of 0.75, 1.5 and 3 mg/kg/day, respectively. This inhibition of metastatic melanoma cell proliferation was partially dependent on disrupting the cytoplasmic membrane, binding to genomic DNA, preventing transcription and translation of the VEGF gene. This inhibition restrained B16F10 migration and angiogenesis. These results further suggest that BF-30 may be a candidate for the treatment of malignant melanoma.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, Jiangsu, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Mengyun
authors.initials: M
authors.lastname: Ke
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Tian
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Dou
authors.forename: Changlin
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D054804:Cathelicidins / Q000008:administration & dosage / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D054804:Cathelicidins; C533044:cathelicidin BF, Bungarus fasciatus; D004247:DNA