Integrative transcriptomic analysis and network pharmacology reveal the anti-ovarian cancer effects of cinchonine in vitro and in vivo

Despite advances in surgery and chemotherapy over recent decades, epithelial ovarian cancer remains the most lethal gynecologic malignancy. Cinchonine, a natural compound traditionally utilized for its anti-inflammatory and anti-malarial properties, has demonstrated anti-tumor activity through multiple pathways. However, its therapeutic potential in epithelial ovarian cancer remains largely unexplored. This study evaluated the anti-tumor effects of cinchonine in epithelial ovarian cancer using both in vitro and in vivo models. In vitro, cinchonine significantly inhibited cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis in selected epithelial ovarian cancer cells. In vivo, cinchonine markedly suppressed tumor growth in an epithelial ovarian cancer xenograft model, with efficacy similar to that of positive control. Histopathological examination revealed no evident toxicity in major organs following cinchonine treatment, whereas cisplatin was associated with mild early toxicity. Integrated transcriptomic and network pharmacology analyses identified the calcium signaling pathway as a key mechanistic axis underlying the effects of cinchonine. Consistent with these findings, in vitro experiments demonstrated that cinchonine significantly increased intracellular calcium ion concentrations in epithelial ovarian cancer cells. Moreover, inhibition of calcium signaling with the specific inhibitor verapamil markedly attenuated the anti-proliferative and pro-apoptotic effects of cinchonine. Collectively, these findings suggest that cinchonine has therapeutic potential for the treatment of epithelial ovarian cancer.