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Artemisinin induced the anti-migratory and anti-invasive effects in Uveal melanoma cells by inhibiting PI3K/AKT/mTOR signaling pathway
Mohd, F.; Zheng, W.
2021-07-01
Source Publication7th macau symposium on Biomedical Science
AbstractUveal melanoma is the most common primary ocular neoplasm in adults, with many patients ending up developing liver metastasis and facing a significant reduction of their life expectancy due to the lack of efficient treatments able to prevent or reduce their occurrence. Artemisinin is an anti-malarial drug that has been widely used in the clinic and whose anticancer properties have also been described. Its reported safety, affordability and ability to reach the ocular tissues point it has a potential therapeutic agent against uveal melanoma. In the present study, we found that a sub-anti-malaria dosage of artemisinin significantly attenuated the migration and invasion potential of uveal melanoma cells, in a concentration-dependent manner. Assessment of the mechanisms underlying artemisinin anticancer action, revealed that its use dramatically reduced the phosphorylation of PI3K, AKT and mTOR in UM cells. Further inhibition of PI3K signaling, using LY294002, or of mTOR, by rapamycin, blocked the migration and invasion of UM cells similarly to artemisinin. In contrast, AKT or mTOR activation (Sc79 or MHY1485, respectively), attenuated the inhibitory effect of artemisinin on the migration and invasion abilities of UM cells, further validating that artemisinin’ anticancer effect is likely to be mediated via inhibition of the PI3K/AKT/mTOR pathway. Artemisinin also induced mitochondrial membrane potential loss and apoptosis of UM cells, having no significant toxic effect in normal retinal neuronal cells RGC-5 and epithelial cells D407. These findings and the fact that the clinical dosage of artemisinin is very safe, strongly suggest that artemisinin is a safe drug for the prevention and treatment of uveal melanomas.
KeywordArtemisinin anti-migratory anti-invasive Uveal melanoma cells PI3K/AKT/mTOR
Language英語English
The Source to ArticlePB_Publication
PUB ID57986
Document TypeConference paper
CollectionDEPARTMENT OF PHARMACEUTICAL SCIENCES
Corresponding AuthorZheng, W.
Recommended Citation
GB/T 7714
Mohd, F.,Zheng, W.. Artemisinin induced the anti-migratory and anti-invasive effects in Uveal melanoma cells by inhibiting PI3K/AKT/mTOR signaling pathway[C], 2021.
APA Mohd, F.., & Zheng, W. (2021). Artemisinin induced the anti-migratory and anti-invasive effects in Uveal melanoma cells by inhibiting PI3K/AKT/mTOR signaling pathway. 7th macau symposium on Biomedical Science.
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