Halorotetin B, A Novel Terpenoid Compound Derived from Marine Ascidian, Suppresses Tumor Growth by Targeting the Cell Cycle Regulator UBE2C

Abstract Screening and identification of novel small‐molecule have proven to be effective strategies in addressing the growing threat of cancer to human health. In this study, a novel natural terpenoid compound, Halorotetin B, is identified from the edible ascidian Halocynthia roretzi . Halorotetin B is shown to significantly inhibit tumor growth both in vitro and in vivo. Mechanistically, the E2 ubiquitin‐conjugating enzyme C (UBE2C) is identified as a direct binding target of Halorotetin B through a combination of the peptide‐centric local stability assay and the omics‐based target enrichment and ranking. Further investigations reveal that Halorotetin B binding to UBE2C induced M phase cell cycle arrest by inhibiting the ubiquitin‐mediated degradation of key cell cycle regulators, including cyclin B1 and securin, ultimately leading to tumor cell senescence. These findings suggest that Halorotetin B, as a novel cell cycle inhibitor targeting UBE2C, holds strong potential for development into ascidian‐derived therapeutics for cancer treatment.