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

  • Adv Sci (Weinh). 2025 Dec 12:e15652. doi: 10.1002/advs.202515652.
Shanhao Han  1 ,  Jianhui Li  1 ,  Yuting Zhu  1 ,  Penghui Liu  1 ,  Yaoyao Zheng  2 ,  Muchun He  3 ,  Bo Dong  1  4  5
Affiliations
  • 1. Fang Zongxi Center for Marine EvoDevo, MoE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, China.
  • 2. Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China.
  • 3. Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China.
  • 4. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.
  • 5. Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, 266003, China.
PMID: 41387196 DOI: 10.1002/advs.202515652
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.

Keywords
Halorotetin B; UBE2C; ascidian; cancer therapy; natural compound.
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