Kim Tae Woo, Ko Seong-Gyu
Department of Biopharmaceutical Engineering, Dongguk University-WISE, Gyeongju 38066, Republic of Korea.
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Antioxidants (Basel). 2024 Dec 14;13(12):1533. doi: 10.3390/antiox13121533.
The extract of the rhizome of Makino has potential anti-cancer and anti-inflammatory effects in many diseases, such as cancer. However, the biological functions of falcarindiol (FAD) in breast cancer are not fully understood. This study proved the anti-inflammatory and anti-cancer effects of FAD in breast cancer. Breast cancer models confirmed that FAD reduces cell viability and decreases the tumor volume of xenograft mouse models in a dose-dependent manner. FAD mediated caspase-3-dependent apoptosis in MDA-MB-231 and MCF-7 cells, whereas Z-VAD-FMK in combination with FAD inhibited caspase-3-induced apoptosis. FAD mediates apoptosis through cytosolic reactive oxygen species (ROS) and calcium (Ca) production and ER stress signaling pathways. In addition, FAD combined with thapsigargin (TG) exerts a synergistic apoptotic cell death effect. In the loss-of-function experiments, PERK or CHOP ablation suppressed intracellular ROS and Ca release and ER stress-induced apoptosis in FAD-treated breast cancer models. Since there is a relationship between ROS and NADPH Oxidase 4 (NOX4), Nox4 ablation blocked ER stress-mediated apoptotic cell death by inhibiting ROS release in FAD-induced breast cancer models. Radioresistant models, such as MCF-7R and MDA-MB-231R, were developed to address the cellular radioresistance in clinical radiotherapy. FAD combined with radiation (2 Gy) overcame radioresistance via the inhibition of the epithelial-mesenchymal transition (EMT) phenomenon, such as the upregulation of PPARγ, , and and the downregulation of . Consequently, these results show that FAD may be a novel treatment as a breast cancer therapy.
牧野根茎提取物在许多疾病（如癌症）中具有潜在的抗癌和抗炎作用。然而，法卡林二醇（FAD）在乳腺癌中的生物学功能尚未完全明确。本研究证实了FAD在乳腺癌中的抗炎和抗癌作用。乳腺癌模型证实，FAD以剂量依赖性方式降低细胞活力并减小异种移植小鼠模型的肿瘤体积。FAD介导MDA - MB - 231和MCF - 7细胞中依赖半胱天冬酶 - 3的凋亡，而Z - VAD - FMK与FAD联合使用可抑制半胱天冬酶 - 3诱导的凋亡。FAD通过胞质活性氧（ROS）和钙（Ca）的产生以及内质网应激信号通路介导凋亡。此外，FAD与毒胡萝卜素（TG）联合使用可发挥协同凋亡细胞死亡作用。在功能缺失实验中，PERK或CHOP基因敲除抑制了FAD处理的乳腺癌模型中的细胞内ROS和Ca释放以及内质网应激诱导的凋亡。由于ROS与NADPH氧化酶4（NOX4）之间存在关系，在FAD诱导的乳腺癌模型中，Nox4基因敲除通过抑制ROS释放阻断了内质网应激介导的凋亡细胞死亡。为解决临床放疗中的细胞放射抗性，构建了放射抗性模型，如MCF - 7R和MDA - MB - 231R。FAD与辐射（2 Gy）联合使用通过抑制上皮 - 间质转化（EMT）现象（如PPARγ等的上调以及[此处原文缺失部分内容]的下调）克服了放射抗性。因此，这些结果表明FAD可能是一种新型的乳腺癌治疗方法。
