Non-cytotoxic nanomolar concentration of arctigenin protects neuronal cells from chemotherapy-induced ferroptosis by regulating SLC7A11-cystine-cysteine axis.

Autor: Li Z; College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing, 100083, China., Cao L; College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing, 100083, China., Han K; College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing, 100083, China., Fan L; College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Haidian District, Beijing, 100193, China. Electronic address: flh@cau.edu.cn., Zhao C; College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing, 100083, China., Yin S; College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing, 100083, China., Hu H; College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua East Road, Haidian District, Beijing, 100083, China.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 May 28; Vol. 710, pp. 149895. Date of Electronic Publication: 2024 Apr 04.
DOI: 10.1016/j.bbrc.2024.149895
Abstrakt: Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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