Hunan Academy of Chinese Medicine, Changsha, 410006, China.
School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China.
Chin J Integr Med. 2024 Nov;30(11):1001-1006. doi: 10.1007/s11655-024-4104-y. Epub 2024 Apr 23.
To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells.
Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC), IC, 2×IC, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay.
Compared to the control group, the 10 (1/2 IC), 20 (IC) and 40 (2×IC) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05).
Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.
研究巴西苏木素诱导乳腺癌细胞发生铁死亡的机制。
将乳腺癌 4T1 细胞分为 6 组：对照组、巴西苏木素 1/2 半数最大抑制浓度（IC）组、IC 组、2×IC 组、依马替尼（10μg/ml）组和卡培他滨（10μg/ml）组。用细胞计数试剂盒-8 法检测巴西苏木素对 4T1 细胞增殖的影响，并筛选巴西苏木素的处理剂量。用电子显微镜评估巴西苏木素对 4T1 细胞线粒体形态的影响以及线粒体损伤。用各种检测试剂盒评估铁、活性氧（ROS）、丙二醛（MDA）、谷胱甘肽（GSH）和谷胱甘肽过氧化物酶 4（GPX4）的水平。用划痕试验和 Transwell 试验检测 4T1 细胞的侵袭和迁移能力。用 Western blot 法检测肿瘤蛋白 p53、溶质载体家族 7 成员 11（SLC7A11）、GPX4 和酰基辅酶 A 合成酶长链家族成员 4（ACSL4）蛋白的表达水平。
与对照组相比，10（1/2 IC）、20（IC）和 40（2×IC）μg/ml 巴西苏木素、依马替尼和卡培他滨组细胞存活率、侵袭和迁移能力、GSH、SLC7A11 和 GPX4 蛋白表达水平以及线粒体体积和嵴降低（P<0.05），线粒体膜密度、Fe、ROS 和 MDA 水平以及 p53 和 ACSL4 蛋白表达水平升高（P<0.05）。
巴西苏木素在乳腺癌细胞中引发铁死亡，其潜在机制主要与 p53/SLC7A11/GPX4 信号通路有关。
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