Germacranolides from Enhydra fluctuans with TRAIL-resistance Abrogating Activity

TRAIL selectively kills cancer cells without harming most normal cells. However, TRAIL resistance is a major problem for its therapeutic use. Developing a strategy to overcome resistance is crucial for the successful use of TRAIL as an antitumor agent. In our screening program of natural products that can abrogate TRAIL resistance, four germacranolides (1–4) were isolated from the aerial parts of Enhydra fluctuans. All compounds exhibited potent TRAIL-resistance overcoming activity against TRAIL-resistant human gastric adenocarcinoma (AGS) cells.