Open Access

Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis

  • Authors:
    • Xiaofeng Liu
    • Yang Hai
    • Jinqu Dong
    • Lan Xu
    • Wenqian Hou
    • Jing Su
    • Weiyu Ren
    • Dongling Liu
  • View Affiliations

  • Published online on: November 1, 2022     https://doi.org/10.3892/ijo.2022.5447
  • Article Number: 157
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

KRAS is a biomarker for non‑small cell lung cancer‑targeted therapy, but there is currently no effective KRAS‑targeting medication. Realgar is an impelling anticancer drug, however its significance in KRAS mutant lung cancer is uncertain. According to our findings, the IC50 of H23 (KRAS mutant) cells is 2.99 times lower than that of H1650 (non‑KRAS mutant) cells. Flow cytometry and the Hoechst 33258 staining assay revealed that H1650 cells treated with 4 µg/ml realgar had an apoptotic rate of 8.2%, while H23 cells had a rate of 21.46%. Accordingly, realgar was more sensitive to KRAS mutant cells. Transcriptome sequencing test indicated that there were 481 different expression genes in H23 cells treated with realgar. In H23 cells treated with realgar, mitochondria shrank, inner membrane folding was disturbed, and mitochondrial membrane potential crushed. Realgar boosted intracellular Fe2+, reactive oxygen species, malondialdehyde and glutathione levels, which were all reversed by ferroptosis inhibitor Fer‑1. Realgar decreased phosphorylated p‑Raf, p‑ERK1/2 and increased p‑p38 and p‑JNK, whereas only p‑Raf was abolished by Fer‑1. Raf inhibitor Sorafenib accelerated the realgar‑induced ferroptosis. On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in anti‑KRAS mutant lung cancer.
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December-2022
Volume 61 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu X, Hai Y, Dong J, Xu L, Hou W, Su J, Ren W and Liu D: Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis. Int J Oncol 61: 157, 2022
APA
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J. ... Liu, D. (2022). Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis. International Journal of Oncology, 61, 157. https://doi.org/10.3892/ijo.2022.5447
MLA
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J., Ren, W., Liu, D."Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis". International Journal of Oncology 61.6 (2022): 157.
Chicago
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J., Ren, W., Liu, D."Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis". International Journal of Oncology 61, no. 6 (2022): 157. https://doi.org/10.3892/ijo.2022.5447