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ORIGINAL RESEARCH article

Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 12 - 2024 | doi: 10.3389/fchem.2024.1478674
This article is part of the Research Topic Discovery and Function Research of Novel Natural Products View all articles

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

Provisionally accepted
He Yang He Yang Ling Wang Ling Wang Mengcheng Zhang Mengcheng Zhang Xingkang Wu Xingkang Wu Zhen-Yu Li Zhen-Yu Li *Kaiqing Ma Kaiqing Ma *
  • Shanxi University, Taiyuan, China

The final, formatted version of the article will be published soon.

    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 result 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.

    Keywords: Acylcarnitine, ferroptosis, CPT-1, colorectal cancer, Stemona alkaloid

    Received: 10 Aug 2024; Accepted: 25 Sep 2024.

    Copyright: © 2024 Yang, Wang, Zhang, Wu, Li and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhen-Yu Li, Shanxi University, Taiyuan, China
    Kaiqing Ma, Shanxi University, Taiyuan, China

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