Репозиторий Университета

© 2021 Spandidos Publications. All rights reserved. Malignant melanomas within the eye present different types of metabolic and metastatic behavior. Uveal melanoma (UM) affects a quarter of a million individuals in the USA; however, the molecular pathogenesis is not well understood. Although UV radiation is a risk factor in cutaneous melanomas, it is not crucial for UM progression. Apart from chromosomal abnormalities, numerous major tumorigenic signaling pathways, including the PI3K/Akt, MAPK/ERK, Ras-association domain family 1 isoform A and Yes-associated protein/transcriptional co-activator with PDZ-binding motif signaling pathways, are associated with intraocular tumors. The present review describes the current insights regarding these signaling pathways that regulate the cell cycle and apoptosis, and could be used as potential targets for the treatment of UMs.

© 2018 Wolters Kluwer Health, Inc. All rights reserved. This work presents the results of in-vitro biological activity studies of three novel anticancer agents, phosphonium salts based on the 3-hydroxypyridine scaffold, including one derivative of 4-deoxypyridoxine. Proliferation and viability of cells treated with these compounds was assessed by the colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Effects of the compounds on apoptosis and cell cycle were studied by flow cytometry using annexin V-FITC/propidium iodide and propidium iodide staining, respectively. The influence of the compounds on mitochondrial membrane potential and intracellular reactive oxygen species was evaluated using tetramethyl rhodamine ethyl and DCFHA staining. Western blot analysis was used to study the changes in the expression of Bcl-xL, Bax, and caspase-3 apoptotic proteins. The treatment of ovarian adenocarcinoma cells OVCAR-4 with the tested compounds inhibited the growth and induced cell cycle arrest in the G1 phase. 3-Hydroxypyridine derivatives induced apoptosis by hyperexpression of Bax and caspase-3, whereas 4-deoxypyridoxine derivative induced cell death partly by reactive oxygen species generation and caspase-3 hyperexpression. These results indicate that the quaternary phosphonium salts studied represent potential therapeutic agents for the treatment of ovarian cancer.