RESUMO
The chloroform extract of the Japanese cypress Chamaecyparis obtusa was found to kill PANC-1 human pancreatic cancer cells preferentially in the nutrient-deprived medium without causing toxicity in the nutrient rich condition. Phytochemical investigation on this extract led to the isolation of a new sesquiterpene (1), together with the six sesquiterpenes (2-7) and a lignan (8). The isolated compounds were tested for their preferential cytotoxicity activity against five different human pancreatic cancer cell lines [PANC-1, MIA PaCa2, CAPAN-1, PSN-1, and KLM-1] by utilizing an antiausterity strategy. Among them, α-cadinol (2) was identified as the most active constituent. α-Cadinol (2) was found to inhibit the activation of Akt/mTOR pathway, and the hyperactivation of autophagy leading to preferential PANC-1 cell death during nutrient-starvation.
Assuntos
Antineoplásicos Fitogênicos/química , Chamaecyparis/química , Ciclodecanos/química , Sesquiterpenos/química , Terpenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Chamaecyparis/metabolismo , Ciclodecanos/isolamento & purificação , Ciclodecanos/toxicidade , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Microscopia de Fluorescência , Conformação Molecular , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/toxicidade , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Terpenos/isolamento & purificação , Terpenos/toxicidadeRESUMO
PURPOSE: Recent work practices in the conservation and restoration involve the use of cyclododecane (CDD, CAS 294-62-2) to protect fragile artifacts during their handling or transportation. Little is known about its toxicity, and no previous exposure has been reported. A short field investigation was conducted to characterize the exposure conditions to both CDD vapors and aerosols. METHODS: Measurements were conducted in the laboratory of conservation and restoration of the archeological service in Bern (Switzerland). Three indoor and four outdoor typical work situations, either during brush or spray gun applications, were investigated. Measurements were performed on charcoal adsorbent tube and analyzed by a gas chromatograph equipped with a flame ionization detector. RESULTS: Measurements have been conducted during both brush and spray gun applications. Indoor exposures were of 0.75-15.5 mg/m(3), while outdoors exposures were 19.5-53.9 mg/m(3). Exposures appear to be extremely localized due to both physicochemical properties and application methods of the CDD. Vapor exposure increases dramatically with the confinement of the workplace. CONCLUSION: Preventive measures should be undertaken to limit as much as possible these exposures. Field work in confined areas (ditches, underground) is of particular concern. CDD-coated artifacts or materials should be stored in ventilated areas to avoid delayed exposures.
Assuntos
Poluentes Ocupacionais do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Arte , Ciclodecanos/análise , Exposição Ocupacional/análise , Poluentes Ocupacionais do Ar/toxicidade , Ciclodecanos/toxicidade , Monitoramento Ambiental , Humanos , Exposição por Inalação/análise , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Exposição Ocupacional/efeitos adversos , VolatilizaçãoRESUMO
A toxicologic and dermatologic review of 1,7,7-trimethylbicyclo[4.4.0]dec-3-yl acetate when used as a fragrance ingredient is presented.
Assuntos
Acetatos/química , Acetatos/toxicidade , Perfumes/química , Perfumes/toxicidade , Acetatos/farmacocinética , Animais , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/farmacocinética , Compostos Bicíclicos com Pontes/toxicidade , Ciclodecanos/química , Ciclodecanos/farmacocinética , Ciclodecanos/toxicidade , Humanos , Perfumes/farmacocinéticaRESUMO
A toxicologic and dermatologic review of tricyclodecanyl acetate when used as a fragrance ingredient is presented.
Assuntos
Acetatos/química , Acetatos/toxicidade , Perfumes/química , Perfumes/toxicidade , Acetatos/farmacocinética , Animais , Ciclodecanos/química , Ciclodecanos/farmacocinética , Ciclodecanos/toxicidade , Humanos , Perfumes/farmacocinética , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
A toxicologic and dermatologic review of tricyclodecenyl acetate when used as a fragrance ingredient is presented.