Pei Sung-Nan, Lee Kuan-Ting, Rau Kun-Ming, Lin Tsung-Ying, Tsai Tai-Hsin, Hsu Yi-Chiang
Department of Hematology Oncology, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan.
Division of Neurosurgery, Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan.
Biomedicines. 2024 Oct 14;12(10):2330. doi: 10.3390/biomedicines12102330.
Luteolin (LUT) is a natural flavonoid with known anti-inflammatory, antioxidant, and anti-cancer properties. Cervical cancer, particularly prevalent in certain regions, remains a significant health challenge due to its high recurrence and poor response to treatment. This study aimed to investigate the anti-tumor effects of LUT on human cervical epidermoid carcinoma cells (Ca Ski), focusing on cell growth inhibition, apoptosis induction, and regulation of mitochondrial membrane potential. Ca Ski cells were treated with varying concentrations of LUT (0, 25, 50, 100 µM) for different time periods (24, 48, 72 hours). Cell viability was measured using the MTT assay, apoptosis was assessed by flow cytometry with annexin V-FITC/PI staining, and changes in mitochondrial membrane potential were evaluated using JC-1 staining. Caspase-3 activation was examined by flow cytometry, and expression of apoptosis-related proteins (caspase-3, -8, -9, AIF) was analyzed via Western blotting. LUT significantly inhibited the growth of Ca Ski cells in a dose- and time-dependent manner, with the most pronounced effects observed at 100 µM over 72 hours. Flow cytometry confirmed that LUT induced apoptosis without causing necrosis. Mitochondrial membrane potential was reduced after LUT treatment, coinciding with increased caspase-3 activation. Western blot analysis revealed the upregulation of pro-apoptotic proteins caspase-3, -8, -9, and AIF, indicating that LUT induces apoptosis through the intrinsic mitochondrial pathway. Luteolin effectively inhibits cervical cancer cell proliferation and induces apoptosis by disrupting mitochondrial membrane potential and activating caspases. These findings suggest that LUT holds potential as a therapeutic agent for cervical cancer, with further studies needed to explore its in vivo efficacy and broader clinical applications.
木犀草素（LUT）是一种具有抗炎、抗氧化和抗癌特性的天然黄酮类化合物。宫颈癌在某些地区尤为普遍，由于其高复发率和对治疗反应不佳，仍然是一个重大的健康挑战。本研究旨在探讨LUT对人宫颈表皮样癌细胞（Ca Ski）的抗肿瘤作用，重点关注细胞生长抑制、凋亡诱导和线粒体膜电位调节。用不同浓度的LUT（0、25、50、100 μM）处理Ca Ski细胞不同时间段（24、48、72小时）。使用MTT法测量细胞活力，通过膜联蛋白V-FITC/PI染色的流式细胞术评估凋亡，并使用JC-1染色评估线粒体膜电位的变化。通过流式细胞术检测半胱天冬酶-3的激活，并通过蛋白质印迹法分析凋亡相关蛋白（半胱天冬酶-3、-8、-9、AIF）的表达。LUT以剂量和时间依赖性方式显著抑制Ca Ski细胞的生长，在72小时时100 μM的效果最为明显。流式细胞术证实LUT诱导凋亡而不引起坏死。LUT处理后线粒体膜电位降低，与半胱天冬酶-3激活增加一致。蛋白质印迹分析显示促凋亡蛋白半胱天冬酶-3、-8、-9和AIF上调，表明LUT通过内在线粒体途径诱导凋亡。木犀草素通过破坏线粒体膜电位和激活半胱天冬酶有效抑制宫颈癌细胞增殖并诱导凋亡。这些发现表明LUT作为宫颈癌治疗剂具有潜力，需要进一步研究以探索其体内疗效和更广泛的临床应用。
