Erythrabyssin ll is identified as a late-stage autophagy inhibitor reversing chemoresistance and promoting apoptosis in ovarian cancer

  • iScience. 2025 Nov 6;28(7):112801. doi: 10.1016/j.isci.2025.112801.
Jing Mo  1  2 ,  Qiling Cai  3 ,  Shanshan Chen  2  4 ,  Jinlan Luo  3 ,  Zhibiao Hu  5 ,  Lili Su  2  6 ,  Lulu Cheng  6 ,  Lijie Huang  2 ,  Shijia Liu  2 ,  Xiangru Wang  2 ,  Qinying Liu  2 ,  Li Chen  3 ,  Shuichun Mao  5 ,  Yang Sun  1  2  6
Affiliations
  • 1. Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
  • 2. Fujian Provincial Key Laboratory of Tumor Biotherapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China.
  • 3. Fujian Provincial Key Laboratory of Medical Instrument and Pharmaceutical Technology, College of Biological Science and Technology, Fuzhou University, Fuzhou 350108, China.
  • 4. Obstetrics and Gynecology Department, Fujian Provincial Hospital, No. 134 East Street, Fuzhou 350001, China.
  • 5. School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
  • 6. Interdisciplinary Institute for Medical Engineering, Fuzhou University, Fuzhou 350108, China.
PMID: 40881620 DOI: 10.1016/j.isci.2025.112801
Abstract

A growing body of research suggests that inhibition of Autophagy may be a novel means of treating Cancer and suppressing drug resistance. Therefore, a series of drugs derived from the Erythrina crista-galli Linn were screened in this study. Among them, the pterocarpan erythrabyssin II (EL-19) is a potent late-stage Autophagy inhibitor, which could effectively block the fusion of autophagosome and lysosome, leading to the accumulation of autophagic substrates in both ovarian Cancer A2780 and A2780/DDP cells. EL-19 did not impair the lysosomal pH and lysosomal enzyme activity. In addition, cell studies, and Organoid experiments showed that EL-19 inhibited the value addition of A2780 and A2780/DDP cells, suppressed ovarian cancer Organoid activity and induced Apoptosis, and blocked cisplatin-induced protective Autophagy in A2780/DDP cells. Combination therapy with DDP superior anti-tumor outcomes compared to monotherapies in animal models. In summary, EL-19 may be developed as an Anticancer agent by blocking chemotherapy-induced protective Autophagy.

Keywords
Biological sciences; Cancer; Clinical pharmacy; Natural product chemistry.
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