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

Summary: 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.