RESUMO
Cigarette smoking is the main cause of chronic obstructive pulmonary disease and lung cancer. The present study was aimed to explore the chemopreventive effect of ursolic acid (UA) on these diseases. In the CSE treated normal human bronchial epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the intracellular redox balance, and relieved the stimulation of external deleterious factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. Moreover, UA inhibited lung cancer development in the model established by A549 cells in nude mice in vivo. For the first time, our results indicate that UA could be developed as a potential lung cancer chemopreventive agent.
Assuntos
Anticarcinógenos/farmacologia , Bronquíolos/patologia , Células Epiteliais/efeitos dos fármacos , Neoplasias Pulmonares/prevenção & controle , Nicotiana/efeitos adversos , Fumaça/efeitos adversos , Triterpenos/farmacologia , Animais , Antineoplásicos Alquilantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Células Cultivadas , Quimioprevenção , Ciclofosfamida/farmacologia , Citoproteção , Dano ao DNA , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Desintoxicação Metabólica Fase II , Camundongos , Camundongos Nus , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Ácido UrsólicoRESUMO
OBJECTIVE: To investigate the protective effect and mechanism of Ecliptae Herba extract on cigarette smoke extract-induced cytotoxicity. METHOD: The effect of Ecliptae Herba extract on CSE-induced NHBE cell proliferation was detected by MTT assay. GSH content was determined by DTNB colorimetry. GST activity was measured by CDNB colorimetric assay. NQO1 activity was detected by NADPH and DCIP. The protein expression was determined by Western blot assay. RESULT: Ecliptae Herba extract reduced CSE's inhibitory effect on NHBE cells, recover the decrease in intracellular GSH caused by CSE and reduce the CSE-induced activity of GST and NQO1 and NQO1 protein expression. CONCLUSION: Ecliptae Herba extract can reduce CSE-induced injury on NHBE cells, which may be related to phase II detoxification enzymes.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Eclipta/química , Nicotiana/química , Substâncias Protetoras/farmacologia , Fumar/efeitos adversos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fumaça/análiseRESUMO
In China, Fusarium head blight is caused mainly by the Fusarium graminearum species complex (FGSC), which produces trichothecene toxins. The FGSC is divided into three chemotypes: 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), and nivalenol (NIV). In order to predict the geographical changes in the distribution of these chemotype populations in major winter wheat-producing areas in China, the biological characteristics of twenty randomly selected isolates from each of the three chemotypes were studied. No significant difference was exhibited in the growth rate of 3-ADON, 15-ADON, and NIV isolates at 15°C. At 20°C and 25°C, the growth rate of 15-ADON isolates was the highest. At 30°C, the growth rate of NIV and 3-ADON isolates was significantly higher than that of 15-ADON isolates. The 15-ADON isolates produced the highest quantities of perithecia and two to three days earlier than the other two populations at each temperature, and released more ascospores at 18°C. The aggressiveness test on wheat seedlings and ears indicated there was no significant difference between the 3-ADON and 15-ADON isolates. However, the aggressiveness of NIV isolates was significantly lower than that of the 3-ADON and 15-ADON isolates. The DON content in grains from heads inoculated with the 3-ADON isolates was higher than the content of 15-ADON and NIV isolates. The results showed that 15-ADON population had the advantage in perithecia formation and ascospore release, and the 3-ADON population produced more DON in wheat grains. We suggested that distribution of these three chemotype populations may be related to these biological characteristics.
Assuntos
Fusarium/genética , Fusarium/fisiologia , Triticum/crescimento & desenvolvimento , China , Fusarium/crescimento & desenvolvimento , Triticum/microbiologiaRESUMO
Here we report a regulatory mechanism by which LKB1 is controlled by 14-3-3 proteins through phorsphorylation of Thr336. The results from the current study indicate that 14-3-3 ζ inhibits LKB1 from phosphorylating its substrate, AMPK (AMP-dependent protein kinase) and attenuates LKB1-mediated G1 cell cycle arrest and apoptosis by interfering with the interaction between LKB1 and its substrates. This regulation does not change either the LKB1 catalytic activity or subcellular localization of LKB1. Moreover, we demonstrate that serum starvation enhances LKB1 activity and increases the phosphorylation of Thr336. Taken together, our results suggest that autophosphorylation of Thr336 acts as an activating signal for LKB1 to recruit 14-3-3, which in turn attenuates the activation of LKB1 to keep the activity of LKB1 in check.