Butyrate attenuates the stemness of lung cancer cells through lysosome Fe 2+ - and SLC7A11-mediated ferroptosis

• Published in: Heliyon Vol. 10; no. 7; p. e28093
• Main Authors: Bi, Rui, Jiang, Lianyong, Hu, Rui, Wen, Bohan, Jiang, Zhaolei, Liu, Hongtao, Mei, Ju
• Format: Journal Article
• Language: English
• Published: England 15-04-2024
• Subjects: Ferroptosis; Lysosome Fe2; SLC7A11; Cancer stem cells; Butyrate
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e28093

Cancer stem cells (CSCs) are considered key contributors to tumor progression, and ferroptosis has been identified as a potential target for CSCs. We have previously shown that butyrate enhances the ferroptosis induced by erastin in lung cancer cell, this study aimed to investigate the impact of butyrate on the progression of lung CSCs. To investigate these effects, we constructed a series of
experiments, including 3D non-adherent sphere-formation, cytometry analysis, assessment of CSC marker expression, cell migration assay, and
tumorigenesis analyses. Additionally, the influence of butyrate on chemotherapeutic sensitivity were determined through both
and
experiments. Mechanistically, immunofluorescence analysis was employed to examine the localization of biotin-conjugated butyrate. We identified that butyrate predominantly localized in the lysosome and concurrently recruited Fe
in lysosome. Moreover, butyrate reduced the stability of SLC7A11 protein stability in lung cancer cells through ubiquitination and proteasome degradation. Importantly, the effects of butyrate on lung CSCs were found to be dependent on lysosome Fe
- and SLC7A11-mediated ferroptosis. In summary, our results demonstrate that butyrate could induce the ferroptosis in lung CSCs by recruiting Fe
in lysosome and promoting the ubiquitination-lysosome degradation of SLC7A11 protein.