RESUMEN
Antrodia salmonea (AS) is a fungus, which belongs to a fungal family of Taiwanofungus salmoneus with the features of anti-oxidant, anti-inflammatory, and anticancer. Recent studies have shown that AS has anti-cancer functions in ovarian and breast cancer. However, the effects of AS on prostate cancer (PCa) proliferation remain unknown. Therefore, we investigated the role of AS in PCa proliferation through apoptosis, and cell cycle regulation in PCa cell lines. Our results showed that Antrodia salmonea extract (ASE) inhibited PCa cells growth with a dose-dependent manner. In addition, ASE decreased the anchorage-independent growth formation ability in PC3 cells. Moreover, ASE-induced cell growth inhibition in PCa cells (DU145, PC3) was correlated to decreased cell cycle-related proteins such as cyclin A/B and cyclin-dependent kinase CDK1/2/4, and increased cell cycle inhibitor proteins p21. Besides, ASE decreased the total protein level of epidermal growth factor receptor and its downstream signaling pathways Akt and Erk in both PCa cells. We found that apoptotic markers such as cleaved-PARP protein levels increased significantly in DU145 cells indicating ASE might induce apoptosis. In conclusion, our results suggest that ASE may have the ability to induce PCa cell death through regulating cell cycle arrest and apoptosis pathways.
Asunto(s)
Apoptosis , Neoplasias de la Próstata , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Humanos , Masculino , Extractos Vegetales/farmacología , Polyporales , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismoRESUMEN
BACKGROUND: Mineral and bone disorder (MBD) is common and associated with mortality in patients with chronic kidney disease (CKD) Given that disarrays in serum phosphorus (P) and parathyroid hormone (PTH) levels and their changes over time are closely interrelated, modeling mortality-predictability of their combinations may help improve CKD patient management. METHODS: A historical cohort study was undertaken to evaluate the joint effect of serum P and PTH levels on mortality in 107,299 chronic hemodialysis (HD) patients. Changes in serum P and PTH levels over 6months, in particular discordant changes, were also modeled with mortality. RESULTS: HD patients were 64±15 (mean±SD)years old and included 45% women, 33% African-American, and 59% diabetic. Compared with serum P level ≥7.0mg/dL and PTH level ≥600pg/mL, adjusted hazard ratio (HR) tended to be lowest in patients with serum P level of 3.5-<5.5mg/dL combined with PTH level of 150-<300pg/mL (HR 0.64, 95% confidence interval 0.61-0.67). A change over time in serum P level towards the 3.5-<5.5mg/dL range from higher or lower ranges was associated with a decreased mortality, whereas only change in PTH level from <150pg/mL to 150-<300pg/mL range was associated with a lower risk of mortality. Upon discordant changes of PTH and P, i.e., decrease in one of the two measures while the other increased, no change in mortality risk was observed. CONCLUSION: In CKD-MBD management, patent survival is the greatest with controlling both serum P and PTH levels in balance. Tailoring an individualized treatment strategy in CKD-MBD may benefit patients. Further studies are needed.
Asunto(s)
Hormona Paratiroidea/sangre , Fósforo/sangre , Diálisis Renal/mortalidad , Anciano , Estudios de Cohortes , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Cigarette smoking causes persistent lung inflammation that is mainly regulated by redox-sensitive pathways. We have reported that cigarette smoke (CS) activates a NADPH oxidase-dependent reactive oxygen species (ROS)-sensitive AMP-activated protein kinase (AMPK) signaling pathway leading to induction of lung inflammation. Glucosamine, a dietary supplement used to treat osteoarthritis, has antioxidant and anti-inflammatory properties. However, whether glucosamine has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model we show that chronic CS exposure for 4 weeks increased lung levels of 4-hydroxynonenal (an oxidative stress biomarker), phospho-AMPK, and macrophage inflammatory protein 2 and induced lung inflammation; all of these CS-induced events were suppressed by chronic treatment with glucosamine. Using human bronchial epithelial cells, we demonstrate that cigarette smoke extract (CSE) sequentially activated NADPH oxidase; increased intracellular levels of ROS; activated AMPK, mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription proteins 3 (STAT3); and induced interleukin-8 (IL-8). Additionally, using a ROS scavenger, a siRNA that targets AMPK, and various pharmacological inhibitors, we identified the signaling cascade that leads to induction of IL-8 by CSE. All these CSE-induced events were inhibited by glucosamine pretreatment. Our findings suggest a novel role for glucosamine in alleviating the oxidative stress and lung inflammation induced by chronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro by inhibiting both the ROS-sensitive NADPH oxidase/AMPK/MAPK signaling pathway and the downstream transcriptional factors NF-κB and STAT3.
Asunto(s)
Antiinflamatorios/administración & dosificación , Glucosamina/administración & dosificación , Neumonía/tratamiento farmacológico , Fumar/efectos adversos , Proteínas Quinasas Activadas por AMP/biosíntesis , Animales , Células Cultivadas , Humanos , Ratones , Estrés Oxidativo/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/patología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Factor de Transcripción STAT3/biosíntesis , Transducción de Señal/efectos de los fármacosRESUMEN
The anthraquinones emodin and aloe-emodin are abundant in rhubarb. Several lines of evidence indicate that emodin and aloe-emodin have estrogenic activity as phytoestrogens. However, their effects on estrogen receptor α (ER α ) activation and breast cancer cell growth remain controversial. The goal of this study is to investigate the effects and molecular mechanisms of emodin and aloe-emodin on breast cancer cell proliferation. Our results indicate that both emodin and aloe-emodin are capable of inhibiting breast cancer cell proliferation by downregulating ER α protein levels, thereby suppressing ER α transcriptional activation. Furthermore, aloe-emodin treatment led to the dissociation of heat shock protein 90 (HSP90) and ER α and increased ER α ubiquitination. Although emodin had similar effects to aloe-emodin, it was not capable of promoting HSP90/ER α dissociation and ER α ubiquitination. Protein fractionation results suggest that aloe-emodin tended to induce cytosolic ER α degradation. Although emodin might induce cytosolic ER α degradation, it primarily affected nuclear ER α distribution similar to the action of estrogen when protein degradation was blocked. In conclusion, our data demonstrate that emodin and aloe-emodin specifically suppress breast cancer cell proliferation by targeting ER α protein stability through distinct mechanisms. These findings suggest a possible application of anthraquinones in preventing or treating breast cancer in the future.
RESUMEN
Cigarette smoke (CS) increases chemokine production in lung epithelial cells (LECs), but the pathways involved are not completely understood. AMP-activated protein kinase (AMPK), a crucial regulator of energy homeostasis, may modulate inflammation. Here, we show that cigarette smoke extract sequentially activated NADPH oxidase; increased intracellular reactive oxygen species (ROS) level; activated AMPK, NF-κB, and STAT3; and induced interleukin 8 (IL-8) in human LECs. Inhibition of NADPH oxidase activation by apocynin or siRNA targeting p47(phox) (a subunit of NADPH oxidase) attenuated the increased intracellular ROS level, AMPK activation, and IL-8 induction. Removal of intracellular ROS by N-acetylcysteine reduced the AMPK activation and IL-8 induction. Prevention of AMPK activation by Compound C or AMPK siRNA lessened the activation of both NF-κB and STAT3 and the induction of IL-8. Abrogation of the activation of NF-κB and STAT3 by BAY11-7085 and AG490, respectively, attenuated the IL-8 induction. We additionally show that chronic CS exposure in mice promoted AMPK phosphorylation and expression of MIP-2α (an IL-8 homolog) in LECs and lungs, as well as lung inflammation, all of which were reduced by Compound C treatment. Thus, a novel NADPH oxidase-dependent, ROS-sensitive AMPK signaling is important for CS-induced IL-8 production in LECs and possibly lung inflammation.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Interleucina-8/biosíntesis , Neumonía/metabolismo , Mucosa Respiratoria/metabolismo , Fumar/efectos adversos , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/genética , Acetofenonas/farmacología , Animales , Línea Celular , Humanos , Interleucina-8/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Extractos Vegetales/administración & dosificación , Neumonía/tratamiento farmacológico , Neumonía/etiología , Pirazoles/farmacología , Pirimidinas/farmacología , ARN Interferente Pequeño/genética , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/patología , Transducción de Señal/efectos de los fármacosRESUMEN
One new compound, 10-hydroxy-gamma-dodecalactone (1) and three natural new compounds, 11-hydroxy-gamma-dodecalactone (2), 2-(2-hydroxyethyl)phenol (3) and 12-hydroxydodecanoic acid methyl ester (4), together with eight known compounds, ergostatrien-3beta-ol, ergosterol peroxide, methyl (4-hydroxyphenyl)acetate, vanillin, 4-hydroxybenzaldehyde, hexadecanoic acid, 5-methoxymethylfuran-2-carbaldehyde and 5-hydroxymethylfuran-2-carbaldehyde, all were isolated from the submerged whole broth of Antrodia camphorata. The structures of 1 and 2 were principally elucidated by spectral evidence and the absolute configuration was elucidated by the modified Mosher's method.