Stemona alkaloid derivative induce ferroptosis of colorectal cancer cell by mediating carnitine palmitoyltransferase 1.

IF 3.8 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Frontiers in Chemistry Pub Date : 2024-10-03 eCollection Date: 2024-01-01 DOI:10.3389/fchem.2024.1478674
He Yang, Ling Wang, Mengcheng Zhang, Xingkang Wu, Zhenyu Li, Kaiqing Ma
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Abstract

Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction.

茎叶生物碱衍生物通过介导肉碱棕榈酰基转移酶1诱导结直肠癌细胞铁变态反应
酰基肉碱的积累是影响脂肪酸代谢的各种代谢紊乱的一个特征。尽管进行了大量研究,但尚未发现通过调节酰基肉碱代谢诱导铁变态反应的特定分子。在本研究中,根据细胞代谢组学研究,确定了在使用 Stemona 生物碱衍生物(SA-11)处理后,酰基肉碱的积累。此外,CPT-1 的水平被证明显著升高,而 CPT-2 的水平则无明显差异,这导致了酰基肉碱的积累。此外,添加外源酰基肉碱后,SA-11 的铁变态诱导能力明显增强,这可能是由于产生了额外的 ROS。与对照组相比,用 SA-11 处理的 HCT-116 细胞中 ROS 水平升高,这也证实了这一假设。这些发现表明,以酰基肉碱代谢为靶点,特别是通过CPT-1,可以通过增强铁变态反应诱导,为癌症治疗提供一种新的治疗策略。
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来源期刊
Frontiers in Chemistry
Frontiers in Chemistry Chemistry-General Chemistry
CiteScore
8.50
自引率
3.60%
发文量
1540
审稿时长
12 weeks
期刊介绍: Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide. Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”. All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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