RESUMO
Usnic acid (UA), a lichen secondary substance, has considerable anticancer activity in vitro, whereas its effect in vivo is limited. Here, potassium usnate (KU) was prepared by the salinization of UA to enhance its water solubility. KU showed increased bioavailability compared with UA in the tumor, liver, and plasma of a CT26 syngeneic mouse tumor xenograft model after oral administration, as determined by LC-MS/MS analysis. KU exhibited potent anticancer effects on colorectal cancer cells and inhibited liver metastasis in an orthotopic murine colorectal cancer model. KU treatment downregulated the epithelial-mesenchymal markers Twist, Snail, and Slug and the metastasis-related genes CAPN1, CDC42, CFL1, IGF1, WASF1, and WASL in cells and tumor tissues. The present results suggest the potential application of the water-soluble form of UA, KU, in anticancer therapy.
Assuntos
Antineoplásicos/administração & dosagem , Benzofuranos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ácido Selênico/farmacocinética , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Benzofuranos/química , Benzofuranos/farmacocinética , Disponibilidade Biológica , Linhagem Celular Tumoral/transplante , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Masculino , Camundongos , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Potássio/química , Ácido Selênico/administração & dosagem , Resultado do TratamentoRESUMO
Selenite(IV) and selenate(VI) are the major forms of Se in aquatic ecosystem. In this study, Pseudorasbora parva were exposed to 10, 200 and 1000⯵gâ¯L-1 selenite and selenate for 28 days. Selenium accumulation, antioxidant enzyme levels, glutathione concentrations, lipid peroxidation and histology were evaluated in livers following exposure. Our results showed that Se(IV) and Se(VI) caused different accumulation patterns in the liver, with a more rapid accumulation of Se with Se(IV) treatment. Both Se species increased hepatic lipid peroxidation after 14 and 28 d (~â¯30%). Among the antioxidants examined, the activity of SOD (except day 28) and the cellular levels of GSH were induced by 72-137% at lower concentrations, while the activity of GST was at least 24% lower than that of the control at 200 and 1000⯵gâ¯L-1 for both Se species at all sampling points. Both forms of Se reduced the hepatosomatic index at 1000⯵gâ¯L-1 after 28 d. In addition, marked histopathological alterations (10-31%) were observed in the liver of P. parva after exposure to both Se species, with higher frequency in the Se(IV) exposed fish. Liver local necrosis was observed only in the liver of fish exposed to 1000⯵gâ¯L-1 of Se(IV) (~â¯20%). Our results suggest that the ecological impacts of dissolved Se in this freshwater species may also contribute to overall toxicity.