Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway
Yan,Fengxia1,2; Liao,Rifang1,3; Silva,Marta1; Li,Shuai1; Jiang,Yizhou1; Peng,Tangming1; Lazarovici,Philip4; Zheng,Wenhua1
Source PublicationJournal of Cellular and Molecular Medicine
AbstractUveal 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, 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.
Keywordcell death FoxO3a nuclear accumulation Pristimerin uveal melanoma
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Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorYan,Fengxia
Affiliation1.Faculty of Health Sciences,University of Macau,Macau,China
2.School of Medical Science,Jinan University,Guangzhou,China
3.Department of pharmacy,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,China
4.Faculty of Medicine,School of Pharmacy Institute for Drug Research,The Hebrew University of Jerusalem,Jerusalem,Israel
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
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GB/T 7714
Yan,Fengxia,Liao,Rifang,Silva,Marta,et al. Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway[J]. Journal of Cellular and Molecular Medicine,2020,24(11):6208-6219.
APA Yan,Fengxia,Liao,Rifang,Silva,Marta,Li,Shuai,Jiang,Yizhou,Peng,Tangming,Lazarovici,Philip,&Zheng,Wenhua.(2020).Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway.Journal of Cellular and Molecular Medicine,24(11),6208-6219.
MLA Yan,Fengxia,et al."Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway".Journal of Cellular and Molecular Medicine 24.11(2020):6208-6219.
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