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BACKGROUND: This study aimed to assess the effects of exogenous SOD administration on prostate cancer cell line (PC-3) apoptosis via the intrinsic pathway by examining the expression of manganese superoxide dismutase (MnSOD), caspase-3, and apoptosis index of the PC-3 cell line. METHODS: We used the prostate cancer cells from secondary prostate cancer cell lines (PC-3) derived from castration refractory prostate cancer (CRPC), cell differentiation grade IV, and had metastasized to the bone from the American Type Culture Collection (ATCC, Rockville, MD, USA). Superoxide dismutase (SOD) is derived from extracts of melon seeds and wheat gliadin biopolymer, and divided into 62.5 mg/mL, 83 mg/mL, 125 mg/mL, and 250 mg/mL doses. Expression of MnSOD was measured by immunohistochemistry (IHC). Expression of caspase-3 was measured using Western Blot method. Apoptotic index is calculated based on the reaction introduction 3OH end of fragmentation of DNA by the enzyme terminal transferase in preparations with TUNEL staining reagents. A one-way ANOVA test and Pearson correlation test were used to determine the relationship between SOD with expression of caspase-3 and apoptotic index. RESULTS: SOD extract significantly increased the expression of caspase-3 (P=0.016) and the apoptotic index (P=0.000) (P<0.05). There was a correlation between the increased doses of SOD extract and the apoptosis index (P=0.015; r=0.679) and between the increased caspase-3 expression and the apoptosis index (P=0.015; r=0.682). CONCLUSION: Administration of superoxide dismutase (SOD) increased apoptosis in a prostate cancer cell line (PC-3) through the increased expression of caspase-3. Superoxide dismutase (SOD) can be considered as a therapy for late-stage prostate cancer that had been progressed to hormone resistant and metastasized and promote apoptosis in those prostate cancer cells.
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INTRODUCTION: Lycopene has been discussed as a potential effector in the prevention and therapy of prostate cancer. It is red, lipophilic and naturally occurring in many fruits and vegetables, such as tomatoes. Several growth factors, including insulin-like growth factor 1 (IGF-1), play important roles in carcinogenesis and metastasis. IGF-1 is a mitogen that plays important roles in the regulation of proliferation, differentiation, and apoptosis. Binding of IGF-1 to its cognate membrane receptor activates Ras/Raf/MAP kinase signaling pathways, which regulate cell-cycle progression, cell survival, and transformation. Lycopene has its protective effect, which affects multiple IGF-1-activated signaling pathways. Lycopene stimulates apoptosis through intrinsic pathways, by stimulating the pro-apoptotic factor of the mitochondrial cavity such as the Bax/Bak protein (an apoptotic promotor). Although tomatoes are widely consumed in Indonesia, there is no research study about the effect of lycopene on prostate cancer in Indonesia. Hence, this study is conducted to measure the influence of lycopene on the level of IGF-1 in Indonesian human prostate cancer cells. MATERIALS AND METHODS: Prostate cancer cells were studied. In this experimental study, cells were taken from patients with Gleason score 6 and divided into 5 groups: 2 control groups and 3 treatment groups, which were given 1 µM, 2 µM and 4 µM of lycopene, respectively. Measurement of mean IGF-1 level was performed by ELISA. A comparative analysis was performed by two-way ANOVA. RESULTS: The result showed that there was a significant difference in mean IGF-1 levels in the provision of various concentrations of lycopene and time of observation (p<0.05). Increased level of mean IGF-1 appeared on 2µM dose of lycopene at 48 hours observation and began to decline in 72 hours observation. This happened also on 4µM lycopene at 24 hours observation and began to decline in 48 hours observation (p<0.05). CONCLUSION: Lycopene could be administered as adjuvant therapy for prostate cancer patients to increase apoptosis, and eventually inhibit the progressivity of cancer cells.
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BACKGROUND: Extracellular matrix degradation may play an important role in the etiology of urethral stricture. MMP1 and TIMP1 are involved in extracellular matrix degradation. The aim of this study was to investigate the roles of MMP1, TIMP1, and MMP1:TIMP1 ratio at the remodeling phase of urethral stricture in an animal model. METHODS: This research was carried out in collaboration between the Bogor Institute of Agriculture, Universitas Indonesia, and the Eijkman Institute Indonesia. This was an experimental in vivo study in adult male New Zealand rabbits, divided into two groups: a urethral stricture group and a control group. Euthanasia was performed in four rabbits of each group on days 7, 14, 21, 28, and 56. Urethral stricture was confirmed with an 8 F urethral catheter. Several laboratory examinations were done, including H&E and Masson trichrome staining, immunohistochemistry, and ELISA, to determine levels of MMP1 and TIMP1. Percentages of total collagen and collagen type 1 were counted with ImageJ 1.46q software. A general linear model was used for statistic analysis. RESULTS: We found that the level of MMP1 was lower, TIMP1 higher, and MMP1:TIMP1 ratio lower in the urethral stricture group than the control group. There was a correlation between MMP1 level with total collagen percentage (r=0.561, P=0.010) and no correlation between TIMP1 and total collagen (r=0.307, P=0.188). CONCLUSION: Imbalance in extracellular matrix degradation was marked by decreased MMP1 level and MMP1:TIMP1 ratio and increased TIMP1 level. This results showed that urethral stricture is not only caused by collagen decomposition, but also by the imbalance of extracellular matrix degradation.
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INTRODUCTION: Urethral stricture is a disease with a high recurrence rate. Angiotensin II via AT1 receptor increases collagen formation through its effects on TGF-ß1 and inhibition of collagenase activity. In this study, we evaluated the antifibrotic effect of angiotensin II receptor blocker on urethral stricture formation by creating a urethral stricture model in a male rabbit. MATERIAL AND METHODS: Thirty three male adult rabbits were separated into 3 groups (control, treatment, and sham). Group I consisted of 15 rabbits with urethral stricture that did not undergo any treatment, group II consisted of 15 rabbits with urethral stricture that were treated with a daily dose of 15 mg/kg losartan, given orally. Group III consisted of 3 rabbits with normal urethra and without any treatment. After 1, 2, and 4 weeks, the urethral tissues were collected, processed, and examined for TGF-ß1, MMP-1, collagen type I, and collagen type III using enzyme-linked immunosorbent assay. Data were analyzed using 2-way analysis of variance using SPSS version 20.0. RESULTS: Urethral TGF-ß1 concentration in the treatment group was significantly lower during the 2nd and 4th week of observation (p<0.0001), MMP-1 was significantly higher in the 1st, 2nd, and 4th week of observation (p<0.0001), collagen type I was significantly lower during the 2nd (p=0.001) and 4th week (p<0.0001), and collagen type III concentration was significantly lower in the 2nd and 4th week of observation (p<0.0001). CONCLUSION: Angiotensin II receptor blocker could limit the progression of urethral stricture. The mechanism may be related to the AT1 blockage that leads to a decrease in TGF-ß1 concentration, eventually resulting in lower collagen concentration due to increased MMP-1 activity.
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AIM: The objective of the study was to compare the efficacy and safety of tamsulosin hydrochloride and doxazosin in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). METHODS: The safety and efficacy of tamsulosin (0.2 mg) and doxazosin (2 mg) was determined after once daily administration for 6 weeks in an open-label, randomized, multicenter study of 101 men with BPH. The International Prostatic Symptom Score (IPSS), maximal urinary flow rates (Qmax), average urinary flow rates (Qave) and residual urine were determined at baseline and again at 6 weeks as efficacy parameters. The primary parameters used for safety evaluation were vital signs (blood pressure and heart rate) and adverse events. The number of patients with a clinically significant response to treatment with tamsulosin or doxazosin was determined and defined as those with >20% improvement from the baseline Qmax or >20% decrease in total IPSS. RESULTS: The total IPSS decreased significantly in both the tamsulosin and doxazosin groups compared to baseline. There was a significant difference in the decrease in total IPSS between two groups. Qmax, Qave and residual urine significantly improved only in the tamsulosin group. There were no significant differences in systolic blood pressure, diastolic blood pressure or heart rate profile in the tamsulosin group; however, doxazosin resulted in a significant difference in systolic and diastolic blood pressure. Tamsulosin was well tolerated; only three patients (6%) in the tamsulosin group reported an adverse event (dizziness) while 11 patients (22%) in the doxazosin group reported an adverse event (dizziness), one of whom withdrew from the study. CONCLUSIONS: Tamsulosin was shown to be more effective than doxazosin in the treatment of LUTS due to BPH.
