title: Chromomycins A2 and A3 from marine actinomycetes with TRAIL resistance-overcoming and Wnt signal inhibitory activities.
abstract: A biological screening study of an actinomycetes strain assembly was conducted using a cell-based cytotoxicity assay. The CKK1019 strain was isolated from a sea sand sample. Cytotoxicity-guided fractionation of the CKK1019 strain culture broth, which exhibited cytotoxicity, led to the isolation of chromomycins A2 (1) and A3 (2). 1 and 2 showed potent cytotoxicity against the human gastric adenocarcinoma (AGS) cell line (IC50 1; 1.7 and 2; 22.1 nM), as well as strong inhibitory effects against TCF/β-catenin transcription (IC50 1; 1.8 and 2; 15.9 nM). 2 showed the ability to overcome tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance. To the best of our knowledge, the effects of chromomycins A2 (1) and A3 (2) on TRAIL resistance-overcoming activity, and on the Wnt signaling pathway, have not been reported previously. Thus, 1 and 2 warrant potential drug lead studies in relation to TRAIL-resistant and Wnt signal-related diseases and offer potentially useful chemical probes for investigating TRAIL resistance and the Wnt signaling pathway.
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. toume@faculty.chiba-u.jp.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Toume
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. kkktt2005@chiba-u.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tsukahara
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. z8p1012@students.chiba-u.jp.
authors.forename: Hanako
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. midori_arai@chiba-u.jp.
authors.forename: Midori A
authors.initials: MA
authors.lastname: Arai
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. mish@chiba-u.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Ishibashi
mesh_terms: D039903:Actinobacteria / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D014128:Chromomycin A3 / Q000302:isolation & purification / Q000494:pharmacology*; D019015:Geologic Sediments / Q000382:microbiology; D006801:Humans; D020128:Inhibitory Concentration 50; D008926:Plicamycin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C000594480:chromomycin A2; D014128:Chromomycin A3; D008926:Plicamycin