Cucurbitacin I induces immunogenic cell death and synergistically potentiates cisplatin efficacy in epithelial ovarian cancer
Epithelial ovarian cancer (EOC) is characterized by a suppressive tumor immune microenvironment (TIME) that undermines therapeutic efficacy. Immunogenic cell death (ICD) is a promising immunotherapy strategy attributed to ameliorating the suppressive TIME. Cisplatin (CDDP), the first-line chemotherapy for EOC, is hindered by cumulative toxicity. Cucurbitacin I (CuI), a bioactive plant-derived compound, exhibits remarkable antitumor activity in preclinical models. However, its ICD-inducing capability and cisplatin-sensitizing potential in EOC remain uninvestigated. This study aims to systematically elucidate the ICD-inducing capability of CuI and its potential to enhance CDDP's antitumor effects in EOC both in vitro and in vivo. The inhibitory effects of CuI on EOC were evaluated at the cellular level. The half-maximal inhibitory concentrations (IC CuI induced caspase-3/GSDME-mediated pyroptosis in EOC cells, driving the release of ICD-related DAMPs, including surface-exposed CRT/ERp57, ATP, and HMGB1. Consequently, CuI-treated EOC cells promoted DC maturation, significantly increasing the proportion of CD80 CuI is a novel ICD inducer that elicits caspase-3/GSDME-mediated pyroptosis and boosts antitumor immunity in EOC. Notably, it enhances the chemosensitivity of EOC to CDDP, offering a promising strategy for EOC treatment.