4,9-二羟基-α-拉帕醌作为一种通过铁死亡发挥作用的三阴性乳腺癌强效抗增殖剂。
4, 9-dihydroxy-α-lapachone as a potent antiproliferation agent for triple-negative breast cancer via ferroptosis.
作者信息
He Zhong, Long Hui, Ma Hongyue, Ran Wanrong, Song Yinhong, Shang Wenjuan, Wang Junhui, Qin Ye, Deng Zhangshuang
机构信息
Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China; State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
出版信息
Fitoterapia. 2025 Jun;183:106567. doi: 10.1016/j.fitote.2025.106567. Epub 2025 Apr 23.
Triple-negative breast cancer (TNBC) is the most aggressive and malignant breast cancer. Ferroptosis is an oxidative, iron-dependent form of regulated cell death. Ferroptosis-targeted therapies is a promising approach to improving treatment outcomes of TNBC. Combining death pathway inhibitors with relevant indices for ferroptosis and LipROS, this study uncovered that a natural product of 4, 9-dihydroxy-α-lapachone (DLN) from Catalpa bungei "jinsi" exhibited in vitro and in vivo inhibitory activity against TNBC via ferroptosis. The molecular mechanism is an activation of the FTH1 led to iron overload, and then inhibition of cysteine-glutamate antiporter (system Xc) and GPX4, which further sensitized TNBC cells to ferroptosis. This study clarified the pathway of DLN-induced cell death in TNBC treatment and exhibited its potential as therapeutic agent for TNBC.
三阴性乳腺癌（TNBC）是最具侵袭性和恶性的乳腺癌。铁死亡是一种氧化的、铁依赖性的程序性细胞死亡形式。靶向铁死亡的疗法是改善TNBC治疗结果的一种有前景的方法。本研究将死亡途径抑制剂与铁死亡和脂质活性氧（LipROS）的相关指标相结合，发现梓树“金丝”中的天然产物4,9-二羟基-α-拉帕醌（DLN）在体外和体内通过铁死亡对TNBC具有抑制活性。其分子机制是FTH1的激活导致铁过载，进而抑制半胱氨酸-谷氨酸反向转运体（系统Xc）和谷胱甘肽过氧化物酶4（GPX4），这进一步使TNBC细胞对铁死亡敏感。本研究阐明了DLN在TNBC治疗中诱导细胞死亡的途径，并展示了其作为TNBC治疗药物的潜力。
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