Shikonin suppresses trophoblast cell growth via regulation of GLI1, and p62 mediated caspase 8 activation

Wang, Yanxi; Zhu, Fangfang; Zhang, Yingxuan; Chen, Chunlin; Lai, Yu‐Ling; Sun, Jianhua; Chen, Si; Pin, Qiu; Gao, Jie; Deng, Gaopi

doi:10.1016/j.reprotox.2020.05.011

Cited by 3 publications

(2 citation statements)

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“…Previously, we demonstrated that shikonin promotes autophagy in HTR-8/SVneo cells. 21 Thus, this study investigated whether shikonin sensitizes cells to ferroptosis via autophagy. Western blotting showed that the combination of RSL3 and shikonin did not alter the protein expression of LC3B or P62 ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

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Shikonin Could Be Used to Treat Tubal Pregnancy via Enhancing Ferroptosis Sensitivity

Lai¹,

Zeng²,

Chen³

et al. 2022

DDDT

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Background Albeit oxidative stress has been implied in the pathogenesis of tubal pregnancy (TP), there are scant data to suggest that ferroptosis occurs in TP. Shikonin plays a pivotal role in redox status, but whether it can regulate ferroptosis to treat TP remains unknown. Methods We collected and analyzed ferroptosis-related indices from the villous tissue (VT) of women suffering from TP and from women with a normal pregnancy. In vitro, we used shikonin and/or RAS-selective lethal 3 (RSL3) to intervene HTR-8/SVneo cells and further detected ferroptosis indices and cell functions. Finally, the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) is pharmacologically activated to explore the effect of Nrf2 on shikonin regulating ferroptosis. Results Increased malondialdehyde content, reduced levels of glutathione and glutathione peroxidase (GPx), and upregulated protein expression which promoted ferroptosis were observed in the VT of TP patients, suggesting that ferroptosis occurred during TP. In vitro, shikonin enhanced ferroptosis sensitivity in HTR-8/SVneo cells induced by RSL3 via amplifying lipid peroxidation, which mainly included increasing cellular reactive oxygen species (ROS), lipid ROS and Fe 2+ level. RSL3 and/or shikonin inhibited Nrf2 and downregulated protein expression of SLC7A11 and GPx4 caused by RSL3 + shikonin co-treatment, which could be reversed under activation of Nrf2. Hence, shikonin facilitated lipid peroxidation by inhibiting Nrf2 signaling. Additionally, shikonin and/or RSL3 potently inhibited the invasion and migration of HTR-8/SVneo cells. Conclusion This study firstly showed that ferroptosis may be involved in TP pathogenesis and shikonin potentially targeted ferroptosis to treat TP.

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Section: Resultsmentioning

confidence: 99%

“…Furthermore, we previously demonstrated that shikonin stimulated autophagy. 21 Autophagy has been reported to promote ferroptosis by degrading ferritin, thereby increasing cellular labile-iron content. 38 However, these results indicated that shikonin sensitized ferroptosis in an autophagy-independent manner.…”

Section: Discussionmentioning

confidence: 99%