Abstract
Colorectal cancer (CRC) is a prevalent malignancy affecting the human digestive tract. Triptonide has been shown to have some anticancer activity, but its effect in CRC is vague. Herein, we examined the effect of triptonide on CRC. In this study, the results of bioinformatics analysis displayed that triptonide may regulate ferroptosis in CRC by modulating GPX4 and SLC7A11. In HCT116 and LoVo cells, the expression levels of GPX4 and SLC7A11 were significantly reduced after triptonide management versus the control group. Triptonide inhibited proliferation, but promoted ferroptosis in CRC cells. SLC7A11 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide inhibited activation of the PI3K/AKT/Nrf2 signaling in CRC cells. Activation of the PI3K/AKT signaling or Nrf2 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide suppressed CRC cell growth in vivo by modulating SLC7A11 and GPX4. In conclusion, Triptonide repressed proliferation and facilitated ferroptosis of CRC cells by repressing the SLC7A11/GPX4 axis through inactivation of the PI3K/AKT/Nrf2 signaling.
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The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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This study was funded by the Natural Science Foundation of Ningxia (No. 2022AAC03571).
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Hai Li designed the study. Weijie Wang and Xiaofen Zhao performed the experiments. Jie Zhou analyzed the data. Weijie Wang wrote the manuscript. All authors have read and approved the final manuscript.
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Wang, W., Zhao, X., Zhou, J. et al. A novel antitumor mechanism of triptonide in colorectal cancer: inducing ferroptosis via the SLC7A11/GPX4 axis. Funct Integr Genomics 24, 126 (2024). https://doi.org/10.1007/s10142-024-01402-2
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DOI: https://doi.org/10.1007/s10142-024-01402-2