Alantolactone triggers oxeiptosis in human ovarian cancer cells via Nrf2 signaling pathway

土木内酯通过 Nrf2 信号通路引发人卵巢癌细胞氧化凋亡

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作者:Mahdieh Nasirzadeh, Somayeh Atari Hajipirloo, Shiva Gholizadeh-Ghaleh Aziz, Yousef Rasmi, Ghader Babaei, Shahriar Alipour

Conclusion

Our results provided evidence that ALT could be a potential option for ovarian cancer treatment by ROS-mediated oxeiptosis.

Methods

MTT assay was used to evaluate the effect of ALT on SKOV3 cell viability. mRNA and protein expression levels of Nrf2 (nuclear factor erythroid 2-related factor 2), KEAP1 (Kelch-like ECH-associated protein 1), PGAM5 (phosphoglycerate mutase family member 5), AIFM1 (Mitochondrial Apoptosis-Inducing Factor), Glutathione synthetase (GSS) and glutathione peroxidase (GPX) were analyzed by real time PCR and western blotting methods respectively.

Results

Our findings showed that ALT inhibits the proliferation of skov3 cells in a time and dose dependent manner and IC50 was 32 μM at 24h.A significant down-regulation of Nrf2, GSH and GPX mRNA levels was seen in skov3 cells incubated with 32 and 64 μM of ALT in comparison with control group, while, mRNA expression levels of PGAM5 and KEAP1 were increased.Western blot analysis showed that ALT significantly decreases protein levels of Nrf2 and increases PGAM5 and KEAP1.ALT dephosphorylated PS116-AIFM1 and total AIFM1 protein level was elevated.

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