Bao Qi, Wang Zihan, Yang Tingting, Su Xiao, Chen Ying, Liu Lifen, Deng Qicheng, Liu Qingyang, Shao Changshun, Zhu Weipei
Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Xuzhou Medical University, Xuzhou, Jiangsu, China.
PLoS One. 2025 Mar 31;20(3):e0319846. doi: 10.1371/journal.pone.0319846. eCollection 2025.
Resistance to chemotherapeutic agents is a critical challenge for the clinical management of ovarian cancer. While curcumin has been reported to possess anti-cancer properties, how it exerts its anti-neoplastic effect on ovarian cancer cells remains to be explored. We here characterized the fate of human ovarian cancer cell lines HO8910 and OVCAR3 treated with curcumin. Cell proliferation, cell death, mitochondrial function, oxidative damage and tumor formation in nude mice were examined. Significant inhibition of proliferation and induction of apoptosis were observed in ovarian cells treated with curcumin. The cancer cells exhibit cell cycle arrest at G2/M phase, mitochondrial accumulation, mitochondrial oxidative stress and high level of DNA damage after curcumin treatment. This effect of curcumin is independent of the BRCA mutation status. Curcumin-induced proliferation inhibition and apoptosis were effectively attenuated by the application of antioxidant N-acetylcysteine (NAC), suggesting that curcumin exerts its anti-cancer effect by inflicting oxidative stress. Curcumin applied at 200 mg/kg intraperitoneal infusion daily also inhibited the growth, oxidative damage, and mitochondrial accumulation of tumor xenografts in vivo. Together, the results indicate that curcumin can exert its anti-tumor effect via inducing mitochondrial dysfunction-associated oxidative DNA damage and can be potentially used in combination with other DNA repair-interfering therapeutics, such as PARP inhibitor, in the treatment of ovarian cancer.
对化疗药物的耐药性是卵巢癌临床治疗的一项严峻挑战。虽然有报道称姜黄素具有抗癌特性，但其如何对卵巢癌细胞发挥抗肿瘤作用仍有待探索。我们在此描述了用姜黄素处理的人卵巢癌细胞系HO8910和OVCAR3的命运。检测了细胞增殖、细胞死亡、线粒体功能、氧化损伤以及裸鼠体内的肿瘤形成情况。在用姜黄素处理的卵巢细胞中观察到增殖受到显著抑制且细胞凋亡增加。姜黄素处理后，癌细胞表现出G2/M期细胞周期阻滞、线粒体聚集、线粒体氧化应激以及高水平的DNA损伤。姜黄素的这种作用与BRCA突变状态无关。应用抗氧化剂N - 乙酰半胱氨酸（NAC）可有效减弱姜黄素诱导的增殖抑制和细胞凋亡，这表明姜黄素通过造成氧化应激发挥其抗癌作用。每天腹腔注射200mg/kg的姜黄素也能抑制体内肿瘤异种移植物的生长、氧化损伤和线粒体聚集。总之，结果表明姜黄素可通过诱导线粒体功能障碍相关的氧化性DNA损伤发挥其抗肿瘤作用，并且在卵巢癌治疗中可能与其他干扰DNA修复的疗法（如PARP抑制剂）联合使用。
