title: Chemosensitizing Effect of Saikosaponin B on B16F10 Melanoma Cells.
abstract: Cancer cell resistance to chemotherapy is one of the obstacles for better cancer treatment, and inflammatory signaling pathways, such as NF-κB signaling pathway, have been recognized to be involved in such chemoresistance. In this study, we aim to identify a new approach for overcoming cancer chemoresistance by using natural compounds. As a result of screening by using Murine B16F10 melanoma cell line constitutively expressing NF-κB luciferase reporter gene, we identified Saikosaponin B2 as an effective inhibitor for etoposide-induced NF-κB activation in B16F10NFkB cells. Saikosaponin B2 sensitized etoposide-induced cell death in B16F10 melanoma cells through the induction of apoptosis. Along with apoptosis induction, we observed an induction of γ-H2AX expression, which is a molecular signature for DNA damage, upon the combination treatment of etoposide and Saikosaponin B2. Among Saikosaponin family compounds, we found that Saikosaponin B1, but not Saikosaponin A, sensitized etoposide-induced cytotoxicity implicating the structural requirement of Saikosaponin B for such chemosensitization. By testing the combination of Saikosaponin B1 and B2 with 9 clinical anticancer drugs, Saikosaponin B showed a certain preference in the combination with those tested anticancer drugs. Collectively, we conclude Saikosaponin B can be an attractive adjuvant for enhancing the clinical effect of cancer chemotherapy.
authors.affiliation: a Division of Pathogenic Biochemistry, Department of Bioscience , Institute of Natural Medicine, University of Toyama , Toyama , Japan.
authors.forename: Heyao
authors.initials: H
authors.lastname: Ma
authors.affiliation: a Division of Pathogenic Biochemistry, Department of Bioscience , Institute of Natural Medicine, University of Toyama , Toyama , Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: a Division of Pathogenic Biochemistry, Department of Bioscience , Institute of Natural Medicine, University of Toyama , Toyama , Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.affiliation: a Division of Pathogenic Biochemistry, Department of Bioscience , Institute of Natural Medicine, University of Toyama , Toyama , Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000633:toxicity; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D012503:Saponins; D005047:Etoposide; D009828:Oleanolic Acid; C025759:saikosaponin D