He Yeying, Tong Jiaying, Li Zijun, Yao Lulu, Chen Chaoyue, Wan Li, Ma Wenyan, Zheng Xiaohui, Cho Namki, Huang Baoyou
Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
Biochim Biophys Acta Mol Basis Dis. 2025 Oct;1871(7):167971. doi: 10.1016/j.bbadis.2025.167971. Epub 2025 Jul 4.
Ovarian cancer (OC) is a highly lethal malignancy in women, often diagnosed at advanced stages. Carboplatin is the primary chemotherapy drug used clinically; however, most patients experience relapse and develop drug resistance after initial treatment, underscoring the urgent need for novel therapeutic strategies. This study investigated the anti-cancer activity and chemo-sensitizing effects of annonacin, an active compound in the fruit extract of Asimina triloba, as well as its underlying mechanisms in OC. Our results demonstrated that annonacin significantly inhibited OC cell viability, DNA replication, and proliferation, while inducing cell cycle arrest and senescence. Additionally, annonacin reduced OC cell-matrix adhesion and suppressed cell migration and invasion. Furthermore, annonacin enhanced the anti-OC efficacy of carboplatin by inducing substantial DNA damage, exhibiting a synergistic anticancer effect. Mechanistically, annonacin exerted potent anti-cancer and anti-migration activities through the p53 signaling pathway-mediated DNA damage response. When combined with carboplatin, this effect was further amplified. In vivo studies showed that annonacin effectively inhibited tumor growth in mice, and its combination with carboplatin demonstrated superior tumor-suppressive capabilities. Acute toxicity assays confirmed that annonacin possesses good biological safety in vivo. Collectively, these findings suggest that annonacin is a promising chemotherapeutic agent for OC treatment and highlight the potential of its combination with carboplatin to improve therapeutic outcomes in OC.
卵巢癌（OC）是女性中一种高度致命的恶性肿瘤，通常在晚期才被诊断出来。卡铂是临床上使用的主要化疗药物；然而，大多数患者在初始治疗后会复发并产生耐药性，这凸显了对新型治疗策略的迫切需求。本研究调查了番荔枝碱的抗癌活性和化疗增敏作用，番荔枝碱是三叶番荔枝果实提取物中的一种活性化合物，以及其在卵巢癌中的潜在作用机制。我们的结果表明，番荔枝碱显著抑制卵巢癌细胞活力、DNA复制和增殖，同时诱导细胞周期停滞和衰老。此外，番荔枝碱降低卵巢癌细胞与基质的粘附，并抑制细胞迁移和侵袭。此外，番荔枝碱通过诱导大量DNA损伤增强了卡铂的抗卵巢癌疗效，表现出协同抗癌作用。从机制上讲，番荔枝碱通过p53信号通路介导的DNA损伤反应发挥强大的抗癌和抗迁移活性。当与卡铂联合使用时，这种效果进一步增强。体内研究表明，番荔枝碱有效抑制小鼠肿瘤生长，其与卡铂联合使用显示出更强的肿瘤抑制能力。急性毒性试验证实，番荔枝碱在体内具有良好的生物安全性。总的来说，这些发现表明番荔枝碱是一种有前景的用于卵巢癌治疗的化疗药物，并突出了其与卡铂联合使用以改善卵巢癌治疗效果的潜力。
