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、p27Kip1, 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.
Skin cancer is one of the primary causes of mortality worldwide.,With an increasing frequency of skin cancers, there is an urgent requirement for the development of numerous treatment options.,The present study investigated the anticancer activity of caffeic acid n-butyl ester (CAE) against the A431 skin cancer cell line.,Antiproliferative effects were investigated using an MMT assay.,Apoptosis was examined by DAPI and Annexin V/fluorescein isothiocyanate and propidium iodide staining.,Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and cell cycle analyses were performed via flow cytometry.,Protein expression was determined by western blotting.,The findings of the present study demonstrated that among a variety of cancer cell lines, CAE exhibited significant anticancer activity against the A431 skin cancer cell line with a half-maximal inhibitory concentration of 20 µM.,CAE was associated with apoptosis and cell cycle arrest of A431 cells, and induced ROS-mediated alterations in MMP.,In addition, CAE considerably suppressed the expression of some of the important proteins of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) cascade.,The results of the present study indicated that CAE exerted anticancer effects on the A431 skin carcinoma cell line via the induction of apoptosis and suppression of the PI3K/AKT/mTOR signaling pathway.,Therefore, CAE may be beneficial for the development of chemotherapy for skin cancers.