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

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

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.
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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