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In-vitro antitumor activity of new quaternary phosphonium salts, derivatives of 3-hydroxypyridine.
Iksanova, Alfiya G; Gabbasova, Raylya R; Kupriyanova, Tatyana V; Akhunzyanov, Almaz A; Pugachev, Michail V; Vafiva, Ruzalia M; Shtyrlin, Nikita V; Balakin, Konstantin V; Shtyrlin, Yurii G.
Afiliación
  • Iksanova AG; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Gabbasova RR; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Kupriyanova TV; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Akhunzyanov AA; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Pugachev MV; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Vafiva RM; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Shtyrlin NV; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Balakin KV; Scientific and Educational Center of Pharmaceutics, Kazan (Volga region) Federal University, Kazan.
  • Shtyrlin YG; Department of Analysis and Scientific Forecasting, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Anticancer Drugs ; 29(7): 682-690, 2018 08.
Article en En | MEDLINE | ID: mdl-29738336
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organofosforados / Piridinas / Ciclo Celular / Apoptosis / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Anticancer Drugs Asunto de la revista: ANTINEOPLASICOS Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organofosforados / Piridinas / Ciclo Celular / Apoptosis / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Anticancer Drugs Asunto de la revista: ANTINEOPLASICOS Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido