Alloxanthin, an autophagy inducer, exhibits potent anti-tumor effects by targeting AKR1C3

The discovery of effective small-molecule compounds represents a promising strategy for cancer therapy. Herein, we identify a terpenoid compound, Alloxanthin, from edible ascidian Halocynthia roretzi . Alloxanthin exhibits dose-dependent inhibitory effects on the proliferation of various tumor cell lines, without showing cytotoxicity toward normal cells. Further experiments reveal that Alloxanthin induced autophagy-dependent cell death without triggering apoptosis. Mechanistic studies demonstrate that the anti-tumor activity of Alloxanthin is mediated through direct binding to Aldo-keto reductase family 1 member C3 (AKR1C3), as confirmed by cellular thermal shift assay (CETSA), enzymatic activity detection, and molecular docking. Taken together, our findings reveal that Alloxanthin, a marine ascidian-derived autophagy inducer, holds potential for development as a lead compound in cancer treatment.