RESUMO
Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Timol/farmacologia , Acetilcisteína/farmacologia , Antracenos/farmacologia , Antineoplásicos Fitogênicos/antagonistas & inibidores , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Transformada , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Sequestradores de Radicais Livres/farmacologia , Humanos , Imidazóis/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Piridinas/farmacologia , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Timol/antagonistas & inibidores , Urotélio/efeitos dos fármacos , Urotélio/metabolismo , Urotélio/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: The aim of this study is to evaluate the diagnostic value of prostate-specific antigen density (PSAD) test in detecting prostate cancer. METHODS: We searched public databases including PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library, and Google scholar before June 2015. In this meta-analysis, specificity, positive LR, negative LR, and dOR of PSAD test in patients with prostate cancer were analyzed from published studies. We applied Meta-DiSc 1.4 and Stata 11.0 software to the meta-analysis. RESULTS: A total of 11 separate studies consisting of 1821 participants were considered in the meta-analysis. The results of this meta-analysis indicated that sensitivity, specificity, positive Likelihood Ratio (LR), negative LR, and Diagnostic Odds Ratio (dOR) of PSAD test for prostate cancer were 0.73 (95% CI = 0.69 to 0.78), 0.64 (95% CI = 0.61 to 0.66), 2.13 (95% CI = 1.64 to 2.76), 0.45 (95% CI = 0.35 to 0.57), and 5.87 (95% CI = 4.42 to 7.81), respectively. It also showed that the AUC and Q* index were 0.77 and 0.71, respectively. The results of the Egger's linear regression test showed that no publication bias existed (p > 0.05). CONCLUSIONS: In general, our results show that specificity, positive LR, negative LR, dOR, the area under the curve (AUC), and Q * index of PSAD test may be appropriate for detecting prostate cancer.
Assuntos
Antígenos de Neoplasias/sangue , Proteínas de Neoplasias/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Área Sob a Curva , Distribuição de Qui-Quadrado , Proteínas Ligadas por GPI/sangue , Humanos , Funções Verossimilhança , Modelos Lineares , Masculino , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapia , Curva ROCRESUMO
Benign prostatic hyperplasia (BPH) is emerging as one of the most common diseases seriously threatening the health of elderly men. Accumulating evidences indicate that hypoxia could induce BPH. However, the underlying mechanism of BPH induced by hypoxia is not clear. In the study, hypoxia-induced autophagy could promote cell survival and endoplasmic reticula stress (ER stress) in WPMY-1 cells. Cell viability induced by hypoxia could been decreased by autophagy inhibitors (3-methyladenine, bafilomycin A1) or siRNA interference in two autophagy genes (Beclin1, ATG5) in WPMY-1 cells. Furthermore, ER stress was present in hypoxia-treated WPMY-1 cells, while autophagy and cell survival could been inhibited by C/EBP-homologous protein siRNA (CHOP), which is an important protein of ER stress pathway. Taken together, our data support a novel model that autophagy as a cytoprotective response promotes cell survival via ER stress under hypoxia in human prostate stromal cells.
Assuntos
Autofagia/fisiologia , Retículo Endoplasmático/fisiologia , Próstata/citologia , Próstata/fisiologia , Estresse Fisiológico/fisiologia , Células Estromais/fisiologia , Hipóxia Celular/fisiologia , Linhagem Celular , Sobrevivência Celular/fisiologia , Humanos , Masculino , Células Estromais/citologiaRESUMO
Squalene synthase (SQS) catalyzes the condensation of two molecules of farnesyl diphosphate to give presqualene diphosphate and the subsequent rearrangement to form squalene. The gene encoding squalene synthase was cloned from Poria cocos by degenerate PCR and inverse PCR. The open reading frame of the gene is 1,497 bp, which encodes 499 amino acid residues. A phylogenetic analysis revealed that P. cocos SQS belonged to the fungus group, and was more closely related to the SQS of Ganoderma lucidum than other fungi. The treatment of P. cocos with methyl jasmonate (MeJA) significantly enhanced the transcriptional level of P. cocos sqs gene and the content of squalene in P. cocos. The transcriptional level of sqs gene was approximately fourfold higher than the control sample and the squalene content reached 128.62 µg/g, when the concentration of MeJA was 300 µM after 72 h induction.
Assuntos
Acetatos/metabolismo , Ciclopentanos/metabolismo , Farnesil-Difosfato Farnesiltransferase/genética , Farnesil-Difosfato Farnesiltransferase/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Oxilipinas/metabolismo , Poria/enzimologia , Esqualeno/metabolismo , Clonagem Molecular , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , Farnesil-Difosfato Farnesiltransferase/biossíntese , Perfilação da Expressão Gênica , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Reação em Cadeia da Polimerase , Poria/genética , Poria/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Regulação para CimaRESUMO
OBJECTIVE: To investigate the protein expression of human testis development related gene 1 (TDRG1) in human testicular cancer and its pathological significance. METHODS: The expression levels of TDRG1 were detected in the testis tissues of testicular cancer patients and normal men by tissue microarray and immunohistochemistry, and the results were analyzed. RESULTS: Immunohistochemistry exhibited positive expression of the TDRG1 protein in the testis of 73.3% (11/15) of the normal men, 83.3% (10/12) of the patients with embryonal carcinoma, 80.0% (8/10) of those with yolk sac tumor, 26.9% (7/26) of those with seminoma, and 57.1% (4/7) of those with teratoma. The expression levels of TDRG1 in the testis tissues of the seminoma and teratoma groups were shown to be significantly lower than that of the normal control (P < 0.01 and P < 0.05), but those of the embryonal carcinoma and yolk sac tumor groups exhibited no significant differences from that of the latter (P > 0.05). CONCLUSION: The significantly reduced expression of the TDRG1 protein in patients with seminoma or teratoma indicates that TDRG1 may be a candidate cancer suppressor gene.