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Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway. | School of Pharmacy

Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway.

Citation:

Fengxia Yan, Liao, Rifang , Silva, Marta , Li, Shuai , Jiang, Yizhou , Peng, Tangming , Lazarovici, Philip , and Zheng, Wenhua . 2020. “Pristimerin-Induced Uveal Melanoma Cell Death Via Inhibiting Pi3K/Akt/Foxo3A Signalling Pathway.”. Journal Of Cellular And Molecular Medicine, 24, 11, Pp. 6208–6219. doi:10.1111/jcmm.15249.

Abstract:

Uveal melanoma (UM) is a highly invasive intraocular malignancy with high mortality. Presently, there is no FDA-approved standard for the treatment of metastatic UM. Pristimerin is a natural quinine methide triterpenoid compound with anti-angiogenic, anti-cancer and anti-inflammatory activities. However, Pristimerin potential cytotoxic effect on UM was poorly investigated. In the present study, we found the migration and invasion of UM-1 cells were inhibited by Pristimerin which also caused a rapid increase of ROS, decreased mitochondrial membrane potential, induced the accumulation of cells in G0/G1 phase, ending with apoptotic cell death. Pristimerin inhibited Akt and FoxO3a phosphorylation and induced nuclear accumulation of FoxO3a in UM-1 cells, increased the expression of pro-apoptotic proteins Bim、p27(Kip1) , cleaved caspase-3, PARP and Bax, and decreased the expression of Cyclin D1 and Bcl-2. LY294002 or Akt-siRNA inhibited the PI3K/Akt/FoxO3a pathway and promoted the Pristimerin-induced apoptosis, while Pristimerin effects were partially abolished in FoxO3a knockdown UM-1 cell cultures. Taken together, present results showed that Pristimerin induced apoptotic cell death through inhibition of PI3K/Akt/FoxO3a pathway in UM-1 cells. These findings indicate that Pristimerin may be considered as a potential chemotherapeutic agent for patients with UM.