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INTRODUCTION: Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation-induced DSB in human prostate cancer cells. MATERIALS AND METHODS: The human prostate cancer PC3 and DU145 cell lines were used. A colony formation assay was performed to analyze the radiation survival of cells. DNA histogram and generation of reactive oxygen species (ROS) were examined using flow cytometry. Western blotting was used to examine the expression of regulatory molecules related to DNA damage repair. RESULTS: Pretreatment with zerumbone enhanced the radiation effect on prostate cancer cells. Zerumbone delayed the abrogation of radiation-induced expression of γ-H2AX, an indicator of DNA DSB. Zerumbone pretreatment markedly reduced ionizing radiation-induced upregulated expression of phosphorylated ATM (ataxia telangiectasia-mutated), which was partially reversed by the ATM agonist methyl methanesulfonate. Ionizing radiation augmented and zerumbone pretreatment reduced the expression of Jak2 and Stat3, which are involved in DNA damage repair signaling. No significant effect on the generation of ROS and expression of ATR was noted after zerumbone treatment. CONCLUSION: Zerumbone sensitized DU145 and PC3 prostatic cancer cells to ionizing radiation by modulating radiation-induced ATM activation during repair of DNA DSBs.
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Reparación del ADN/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Tolerancia a Radiación/efectos de los fármacos , Sesquiterpenos/farmacología , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Línea Celular Tumoral , Roturas del ADN de Doble Cadena/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Histonas/metabolismo , Humanos , Janus Quinasa 2/metabolismo , Masculino , Células PC-3 , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/radioterapia , Radiación Ionizante , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: There was no consensus about the management of patients with urinary retention and elevated serum prostate-specific antigen (PSA) levels. This study aimed to determine whether concomitant transrectal ultrasound (TRUS)-guided biopsy and transurethral resection of prostate (TURP) is practical in patients with urinary retention and elevated serum PSA levels. METHODS: From March 2007 to May 2015, a total of 34 patients with urinary retention and elevated PSA (≥ 4 ng/mL) underwent concomitant TRUS-guided biopsy and TURP. The medical records were evaluated retrospectively, and data including PSA, prostate volume, TURP results, TRUS-guided biopsy results, length of hospitalization, and complications were collected. These patients were then compared with 40 patients with urinary retention who underwent TURP alone. RESULTS: The mean age of the patients was 71.6 years. The mean PSA levels were 16.9 ng/mL. Prostate cancer was detected in eight cases (23.5%): one case by TRUS-guided biopsy alone, two cases by TURP alone, and five cases by both TRUS-guided biopsy and TURP. Complications included fever in five patients (14.7%), recatheterization for urine retention in two patients (5.9%), urinary tract infection in two patients (5.9%), and de novo urge incontinence in seven patients (20.6%). The complication rate was not significantly increased compared with that of the patients who underwent TURP alone. CONCLUSION: This study showed that concomitant TRUS-guided biopsy and TURP was safe and of possible clinical significance in urinary retention patients with elevated serum PSA.
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Biopsia Guiada por Imagen/métodos , Antígeno Prostático Específico/sangre , Próstata/patología , Resección Transuretral de la Próstata/métodos , Ultrasonografía Intervencional , Retención Urinaria/cirugía , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resección Transuretral de la Próstata/efectos adversosRESUMEN
Prostate cancer is the fifth most common cancer overall in the world. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, most prostate cancer patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant tumors within 1-3 years after treatment. The median overall survival time is 1-2 years after tumor relapse. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling, indicating that inhibition of PI3K/Akt might be a potential therapy for advanced prostate tumors. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. CAPE is a well-known NF-κB inhibitor. CAPE has been used in folk medicine as a potent anti-inflammatory agent. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. We discuss the potential of using CAPE as a treatment for patients with advanced prostate cancer targeting Akt signaling pathway in this review article.
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Prostate carcinoma is one of the most common malignant tumors and has become a more common cancer in men. Previous studies demonstrated that evodiamine (EVO) exhibited anti-tumor activities on several cancers, but its effects on androgen-independent prostate cancer are unclear. In the present study, the action mechanisms of EVO on the growth of androgen-independent prostate cancer cells (DU145 and PC3 cells) were explored. EVO dramatically inhibited the growth and elevated cytotoxicity of DU145 and PC3 cells. The flow cytometric analysis of EVO-treated cells indicated a block of G2/M phase and an elevated level of DNA fragmentation. The G2/M arrest was accompanied by elevated Cdc2 kinase activity, an increase in expression of cyclin B1 and phosphorylated Cdc2 (Thr 161), and a decrease in expression of phosphorylated Cdc2 (Tyr 15), Myt-1, and interphase Cdc25C. TUNEL examination showed that EVO-induced apoptosis was observed at 72 h. EVO elevated the activities of caspase 3, 8, and 9 in DU145 cells, while in PC3 cells only the activities of caspase 3 and 9 were elevated. EVO also triggered the processing of caspase 3 and 9 in both DU145 and PC3 cells. We demonstrate that roscovitine treatment result in the reversion of G2/M arrest in response to EVO in both DU145 and PC3. However, inhibitory effect of roscovitine on EVO-induced apoptosis could only be observed in DU145 rather than PC3. In DU145, G2/M arrest might be a signal for initiation of EVO-triggered apoptosis. Whereas EVO-triggered PC3 apoptosis might be independent of G2/M arrest. These results suggested that EVO inhibited the growth of prostate cancer cell lines, DU145 and PC3, through an accumulation at G2/M phase and an induction of apoptosis.
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Andrógenos/fisiología , División Celular/efectos de los fármacos , Extractos Vegetales/toxicidad , Quinazolinas/toxicidad , Apoptosis/efectos de los fármacos , Proteína Quinasa CDC2/antagonistas & inhibidores , Proteína Quinasa CDC2/metabolismo , Carcinoma/patología , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Medios de Cultivo/química , Ciclina B/metabolismo , Ciclina B1 , Fragmentación del ADN/efectos de los fármacos , ADN de Neoplasias/metabolismo , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Fase G2/efectos de los fármacos , Humanos , L-Lactato Deshidrogenasa/análisis , L-Lactato Deshidrogenasa/metabolismo , Masculino , Neoplasias de la Próstata/patología , Purinas/farmacología , RoscovitinaRESUMEN
INTRODUCTION: This randomized prospective study was conducted to compare the efficacy and safety of the Gyrus Plasmasect loop bipolar transurethral resection of prostate (TURP) and conventional monopolar TURP in the treatment of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 117 men were enrolled in this study. Fifty-eight patients underwent Gyrus Plasmasect TURP and 59 patients underwent monopolar TURP. They were followed up for 3 months after surgery. RESULTS: Significant improvements were seen postoperatively in both the Gyrus and monopolar groups in terms of prostatic volume, International Prostate Symptom Score, quality of life score, peak flow rate, and post-void residual urine volume. However, the degree of improvement was not statistically different between the 2 groups. Significantly less blood loss, shorter postoperative catheterization time and length of hospital stay were seen in the Gyrus group. CONCLUSIONS: Gyrus Plasmasect TURP yielded comparable results to monopolar TURP; however, this is only a preliminary study and follow-up is necessary to assess its long-term efficacy.