IMCA Induces Ferroptosis Mediated by SLC7A11 through the AMPKmTOR Pathway in Colorectal Cancer
Joint Authors
Li, Yanzhang
Teng, Tie-Shan
Zhang, Lei
Wang, Qun
Liu, Fangyan
Liu, Wen
Song, Mengjiao
Yu, Qi
Tang, Kun
Wu, Dongdong
Wang, Xijing
Han, Wuqi
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-04
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Ferroptosis, implicated in several diseases, is a new form of programmed and nonapoptotic cell death triggered by iron-dependent lipid peroxidation after inactivation of the cystine/glutamate antiporter system xc–, which is composed of solute carrier family 7 membrane 11 (SLC7A11) and solute carrier family 3 membrane 2 (SLC3A2).
Therefore, inducing ferroptosis through inhibiting the cystine/glutamate antiporter system xc– may be an effective way to treat cancer.
In previous screening tests, we found that the benzopyran derivative 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) significantly inhibited the viability of colorectal cancer cells.
However, the impact of IMCA on ferroptosis remains unknown.
Hence, this study investigated the effect of IMCA on ferroptosis and elucidated the underlying molecular mechanism.
Results showed that IMCA significantly inhibited the cell viability of colorectal cancer cells in vitro and inhibited tumor growth with negligible organ toxicity in vivo.
Further studies showed that IMCA significantly induced the ferroptosis of colorectal cancer cells.
Mechanistically, IMCA downregulated the expression of SLC7A11 and decreased the contents of cysteine and glutathione, which resulted in reactive oxygen species accumulation and ferroptosis.
Furthermore, overexpression of SLC7A11 significantly attenuated the ferroptosis caused by IMCA.
In addition, IMCA regulated the activity of the AMPK/mTOR/p70S6k signaling pathway, which is related to the activity of SLC7A11 and ferroptosis.
Collectively, our research provided experimental evidences on the activity and mechanism of ferroptosis induced by IMCA and revealed that IMCA might be a promising therapeutic drug for colorectal cancer.
American Psychological Association (APA)
Zhang, Lei& Liu, Wen& Liu, Fangyan& Wang, Qun& Song, Mengjiao& Yu, Qi…[et al.]. 2020. IMCA Induces Ferroptosis Mediated by SLC7A11 through the AMPKmTOR Pathway in Colorectal Cancer. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1203781
Modern Language Association (MLA)
Zhang, Lei…[et al.]. IMCA Induces Ferroptosis Mediated by SLC7A11 through the AMPKmTOR Pathway in Colorectal Cancer. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1203781
American Medical Association (AMA)
Zhang, Lei& Liu, Wen& Liu, Fangyan& Wang, Qun& Song, Mengjiao& Yu, Qi…[et al.]. IMCA Induces Ferroptosis Mediated by SLC7A11 through the AMPKmTOR Pathway in Colorectal Cancer. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1203781
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203781