Cephaeline promotes ferroptosis by targeting NRF2 to exert anti-lung cancer efficacy.

IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Pharmaceutical Biology Pub Date : 2024-12-01 Epub Date: 2024-02-09 DOI:10.1080/13880209.2024.2309891
Peng Chen, Qingxuan Ye, Shang Liang, Linghui Zeng
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引用次数: 0

Abstract

Context: Cephaeline is a natural product isolated from ipecac (Cephaelis ipecacuanha [Brot.] A. Rich. [Rubiaceae]). It exhibits promising anti-lung cancer activity and ferroptosis induction may be a key mechanism for its anti-lung cancer effect.

Objectives: This study investigates the anti-lung cancer activity and mechanisms of cephaeline both in vitro and in vivo.

Materials and methods: H460 and A549 lung cancer cells were used. The cephaeline inhibition rate on lung cancer cells was detected via a Cell Counting Kit-8 assay after treatment with cephaeline for 24 h. Subsequently, the concentrations of 25, 50 and 100 nM were used for in vitro experiments. In addition, the antitumour effects of cephaeline (5, 10 mg/kg) in vivo were evaluated after 12 d of cephaeline treatment.

Results: Cephaeline showed significant inhibitory effects on lung cancer cells, and the IC50 of cephaeline on H460 and A549 at 24, 48 and 72 h were 88, 58 and 35 nM, respectively, for H460 cells and 89, 65 and 43 nM, respectively, for A549 cells. Meanwhile, we demonstrated that ferroptosis is the key mechanism of cephaeline against lung cancer. Finally, we found that cephaeline induced ferroptosis in lung cancer cells by targeting NRF2.

Discussion and conclusion: We demonstrated for the first time that cephaeline inhibits NRF2, leading to ferroptosis in lung cancer cells. These findings may contribute to the development of innovative therapeutics for lung cancer.

Cephaeline通过靶向NRF2促进铁变态反应,从而发挥抗肺癌功效。
背景:Cephaeline是从ipecac(Cephaelis ipecacuanha [Brot.] A. Rich. [茜草科])中分离出来的一种天然产物。它具有良好的抗肺癌活性,诱导铁变态反应可能是其抗肺癌作用的关键机制:材料与方法:采用 H460 和 A549 肺癌细胞。材料和方法:采用 H460 和 A549 肺癌细胞,用细胞计数试剂盒-8 检测头孢噻肟处理 24 小时后对肺癌细胞的抑制率。此外,在使用西非林(5、10 毫克/千克)治疗 12 天后,还对其体内抗肿瘤效果进行了评估:结果:西法林对肺癌细胞有明显的抑制作用,在 24、48 和 72 小时内,西法林对 H460 和 A549 细胞的 IC50 分别为 88、58 和 35 nM,对 A549 细胞的 IC50 分别为 89、65 和 43 nM。同时,我们还证明了铁突变是头孢菲林抗肺癌的关键机制。最后,我们发现头孢氨苄通过靶向 NRF2 诱导肺癌细胞的铁凋亡:我们首次证明了头孢菲林能抑制 NRF2,从而导致肺癌细胞的铁蛋白沉着。这些发现可能有助于开发治疗肺癌的创新疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmaceutical Biology
Pharmaceutical Biology 医学-药学
CiteScore
6.70
自引率
2.60%
发文量
191
审稿时长
1 months
期刊介绍: Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine. Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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