RESUMEN
Paeonol (Pae) is the main active ingredient from the root bark of Paeonia moutan and the grass of Radix Cynanchi Paniculati. Numerous reports indicate that Pae effectively inhibits several types of cancer lines. In this study, we report that Pae hinders prostate cancer growth both in vivo and in vitro. Human prostate cancer lines DU145 and PC-3 were cultured in the presence of Pae. The xenograft tumor in mice was established by subcutaneous injection of DU145 cells. Cell growth was measured by MTT, and the apoptosis was detected by the flow cytometry. Expression of Bcl-2, Bax, Akt, and mTOR were tested by western blotting assay. DU145 and PC-3 showed remarkable sensitivity to Pae, and exposure to Pae induced dose-and time-dependent growth inhibitory responses. Moreover, treatment of Pae promoted apoptosis and enhanced activities of caspase-3, caspase-8, and caspase-9 in DU145. Further work demonstrated Pae reduced expression of Bcl-2 and increased expression of Bax in DU145. Interestingly, we observed that Pae significantly decreased phosphorylated status of Akt and mTOR, and inhibitory effects of Pae and PI3K/Akt inhibitor on DU145 proliferation were synergistic. Finally, we confirmed that oral administration of Pae to the DU145 tumor-bearing mice significantly lowered tumor cell proliferation and led to tumor regression. Pae possesses inhibitory effects on prostate cancer cell growth both in vitro and in vivo, and the anti-proliferative effect may be closely related to its activation of extrinsic and intrinsic apoptotic pathway and inhibition of the PI3K/Akt pathway (AU)
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Asunto(s)
Humanos , Animales , Masculino , Ratones , Suplementos Dietéticos , Acetofenonas/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Antineoplásicos Fitogénicos/uso terapéutico , Estructuras de las Plantas/química , Lamiales/química , Paeonia/química , Medicina Tradicional China , Absorción Intestinal , Fenómenos Fisiológicos Celulares , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Paeonol (Pae) is the main active ingredient from the root bark of Paeonia moutan and the grass of Radix Cynanchi Paniculati. Numerous reports indicate that Pae effectively inhibits several types of cancer lines. In this study, we report that Pae hinders prostate cancer growth both in vivo and in vitro. Human prostate cancer lines DU145 and PC-3 were cultured in the presence of Pae. The xenograft tumor in mice was established by subcutaneous injection of DU145 cells. Cell growth was measured by MTT, and the apoptosis was detected by the flow cytometry. Expression of Bcl-2, Bax, Akt, and mTOR were tested by western blotting assay. DU145 and PC-3 showed remarkable sensitivity to Pae, and exposure to Pae induced dose-and time-dependent growth inhibitory responses. Moreover, treatment of Pae promoted apoptosis and enhanced activities of caspase-3, caspase-8, and caspase-9 in DU145. Further work demonstrated Pae reduced expression of Bcl-2 and increased expression of Bax in DU145. Interestingly, we observed that Pae significantly decreased phosphorylated status of Akt and mTOR, and inhibitory effects of Pae and PI3K/Akt inhibitor on DU145 proliferation were synergistic. Finally, we confirmed that oral administration of Pae to the DU145 tumor-bearing mice significantly lowered tumor cell proliferation and led to tumor regression. Pae possesses inhibitory effects on prostate cancer cell growth both in vitro and in vivo, and the anti-proliferative effect may be closely related to its activation of extrinsic and intrinsic apoptotic pathway and inhibition of the PI3K/Akt pathway.
Asunto(s)
Acetofenonas/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Suplementos Dietéticos , Neoplasias de la Próstata/dietoterapia , Acanthaceae/química , Acetofenonas/administración & dosificación , Acetofenonas/sangre , Acetofenonas/metabolismo , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/sangre , Antineoplásicos Fitogénicos/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Etnofarmacología , Humanos , Absorción Intestinal , Masculino , Medicina Tradicional China , Ratones Desnudos , Paeonia/química , Corteza de la Planta/química , Componentes Aéreos de las Plantas/química , Raíces de Plantas/química , Poaceae/química , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Distribución Aleatoria , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To investigate nephroprotective effects of a mixture of 8 L-amino acids on renal ischemia-reperfusion injury and its effects on renal endothelin-1 (ET-1). METHODS: The mixture of 8 L-amino acids includes glycine, alanine, threonine, serine, valine, leucine, isoleucine and proline. Acute ischemic renal injury was induced by clamping renal pedicle for 45 minutes in rats. Sixty male Sprague-Dawley rats were randomly divided into 3 groups: a sham-operated group (Group A, n=8), a control group (Group B, n=26) and an amino acid-treated group (Group C, n=26). Amino acids were infused at a rate of 1 ml x 100g(-1) x h(-1) I hour before ischemia and during 3 hours of the whole reperfusion. The serum creatinine values, BUN levels, creatinine clearance, urine sodium and potassium excretion, urine lactate dehydrogenase (LDH), the rate of urine flow and histological examination were measured. Renal ET-1 levels were assayed with radioimmunological assay (RIA) RESULTS: The creatinine clearance was 471.0 microl/min+/-121.5 microl/min in Group C and 227.0 microl/min+/-27.0 microl/min in Group B 3 hours after reperfusion, P<0.01). The urine flow rate was 63.6 microl/min+/-15.2 microl/min in Group C and 24.3 microl/min+/-7.7 microl/minin Group B, P<0.01) 1.5 hours after reperfusion. The serum creatinine was 85.0 microl/min+/-7.7 micromol/L and BUN concentration 11.4 mmol/L+/-3.9 mmol/L in Group C and 112.7 micromol/L+/-19.5 micromol/L and 20.7 mmol/L+/-6.6 mmol/L respectively in Group B after 24 hours of reperfusion (P<0.05). The mean histological score by standards of Paller in kidneys was 108.7+/-15.7 in Group C, and 168.8+/-14.8in Group B (P<0.01). The renal ET-1 levels 15 minute and 3 hours after reperfusion were 7.2 pg/mg+/-0.8 pg/mg and 9.6 pg/ml+/-1.0 pg/ml in Group C, and 10.1 pg/ml+/-2.8 pg/ml and 13.0 pg/ml+/-2.7pg/ml in Group B (P<0.01). CONCLUSIONS: The mixture of 8 L-amino acids can provide remarkable protection against renal ischemia-reperfusion injury in rats. This may associate with attenuation of renal ET-1 disorder.