Isolation of Resistomycin from a Terrestrial Actinomycete with TRAIL Resistance-overcoming Activity

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) potently induces apoptosis in most cancer cells, but not in normal cells, and, thus, has attracted intense interest as a promising antitumor agent. Activity-guided fractionation of the culture broth of the actinomycete CKK1172 strain led to the isolation of the antibiotic resistomycin (1) using human gastric adenocarcinoma AGS cells. Compound 1 exhibited TRAIL resistance-overcoming activity at 2 μM with 38% more inhibition than a treatment with 1 alone (without TRAIL) in TRAIL-resistant AGS cells.