Chromomycins A2 and A3 from Marine Actinomycetes with TRAIL Resistance-Overcoming and Wnt Signal Inhibitory Activities

Marine Drugs

Kazufumi Toume¹  Kentaro Tsukahara¹  Hanako Ito¹  Midori A. Arai¹ 

[1] Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan;

关键词: chromomycin A₂;    chromomycin A₃;    actinomycetes;    TRAIL;    Wnt;   

DOI  :  10.3390/md12063466

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.