Eanes Lauren A, Eldeeb Mayar, Storholt Darrell, Patel Yashomati M
Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America.
PLoS One. 2025 Apr 3;20(4):e0320020. doi: 10.1371/journal.pone.0320020. eCollection 2025.
Breast cancer is the second leading cause of cancer deaths among women. While tamoxifen, a commonly used drug therapy in breast cancer patients, is effective, many patients acquire tamoxifen resistance. Therefore, it is essential to identify alternative or combination therapeutics for the treatment of breast cancer. Naringenin, a naturally occurring flavonoid, has been reported to elicit antioxidant, anti-proliferative, and pro-apoptotic effects in cancer cells. The current study aimed to identify the mechanism by which naringenin induces apoptosis in tamoxifen-resistant breast cancer cells. The present study demonstrated that naringenin induced an increase in ROS, resulting in oxidative stress, impaired mitochondrial function, and apoptosis in tamoxifen-resistant breast cancer cells. Our study reports that naringenin specifically increases mitochondrial superoxide anions and hydrogen peroxide production while also causing mitochondrial dysfunction. These studies provide novel evidence for the mechanism by which naringenin induces apoptosis in tamoxifen-resistant breast cancer cells and supports the use of naringenin as a therapeutic on breast cancer cells and drug-resistant cancer cells.
乳腺癌是女性癌症死亡的第二大主要原因。虽然他莫昔芬是乳腺癌患者常用的药物治疗方法，且效果显著，但许多患者会产生他莫昔芬耐药性。因此，确定治疗乳腺癌的替代疗法或联合疗法至关重要。柚皮素是一种天然存在的类黄酮，据报道它在癌细胞中具有抗氧化、抗增殖和促凋亡作用。本研究旨在确定柚皮素诱导他莫昔芬耐药乳腺癌细胞凋亡的机制。本研究表明，柚皮素会导致活性氧增加，从而引起氧化应激、线粒体功能受损以及他莫昔芬耐药乳腺癌细胞凋亡。我们的研究报告称，柚皮素会特异性增加线粒体超氧阴离子和过氧化氢的产生，同时还会导致线粒体功能障碍。这些研究为柚皮素诱导他莫昔芬耐药乳腺癌细胞凋亡的机制提供了新证据，并支持将柚皮素用作治疗乳腺癌细胞和耐药癌细胞的药物。
