School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001 China.
Bioorg Chem. 2023 Apr;133:106415. doi: 10.1016/j.bioorg.2023.106415. Epub 2023 Feb 9.
As one of the mycotoxins produced by Aspergillus fumigatus, gliotoxin has a variety of pharmacological effects, such as anti-tumor, antibacterial, immunosuppressive. Antitumor drugs induce tumor cell death in several forms, including apoptosis, autophagy, necrosis and ferroptosis. Ferroptosis is a recently identified unique form of programmed cell death characterized by iron-dependent accumulation of lethal lipid peroxides, which induces cell death. A large amount of preclinical evidence suggests that ferroptosis inducers may enhance the sensitivity of chemotherapy and the induction of ferroptosis may be an effective therapeutic strategy to prevent acquired drug resistance. In our study, gliotoxin was characterized as a ferroptosis inducer and showed strong anti-tumor activity with IC of 0.24 μM and 0.45 μM in H1975 and MCF-7 cells at 72 h, respectively. Gliotoxin may provide a new natural template for the designing of ferroptosis inducers.
作为烟曲霉产生的一种真菌毒素，曲酸具有多种药理学作用，如抗肿瘤、抗菌、免疫抑制。抗肿瘤药物以多种形式诱导肿瘤细胞死亡，包括细胞凋亡、自噬、坏死和铁死亡。铁死亡是一种最近发现的独特的程序性细胞死亡形式，其特征是铁依赖性累积致死性脂质过氧化物，从而诱导细胞死亡。大量临床前证据表明，铁死亡诱导剂可能增强化疗的敏感性，诱导铁死亡可能是预防获得性耐药的有效治疗策略。在我们的研究中，曲酸被鉴定为铁死亡诱导剂，在 72 小时时，其对 H1975 和 MCF-7 细胞的 IC 分别为 0.24 μM 和 0.45 μM，显示出很强的抗肿瘤活性。曲酸可能为铁死亡诱导剂的设计提供了新的天然模板。
