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1.
Phytomedicine ; 17(5): 363-8, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19748259

ABSTRACT

It is well known that the garlic-derived organosulfur compounds (OSCs) are effective to inhibit a variety of human cancers such as prostate, breast, colon, skin, lung, and bladder cancers. Herein, the pro-apoptotic effects of diallyl trisulfide (DATS), one of garlic-derived OSCs, on T24 bladder cancer cells were investigated. The results demonstrated that DATS suppressed proliferation of T24 bladder cancer cells in a dose- and time-dependent manner which was associated with induced G2/M Phase cell cycle arrest and apoptosis. Mechanistically, DATS inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that DATS may be an effective way for treating human bladder and other types of cancers.


Subject(s)
Allyl Compounds/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Garlic/chemistry , Plant Extracts/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Sulfides/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Allyl Compounds/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Down-Regulation , Humans , Phosphorylation/drug effects , Phytotherapy , Plant Extracts/pharmacology , Protein Kinases/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Sulfides/pharmacology , Urinary Bladder Neoplasms/metabolism
2.
Cancer Sci ; 101(2): 488-93, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20028382

ABSTRACT

Resveratrol, a naturally occurring polyphenolic antioxidant compound present in grapes and red wine, has been reported to hold various biochemical responses. In this preliminary study, we evaluate the chemopreventive potential of resveratrol against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with resveratrol resulted in a significant decrease in cell viability. Resveratrol induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 9 and caspase 3 followed by poly(ADP-ribose) polymerase degradation. Treatment with resveratrol led to G(1) phase cell cycle arrest in T24 cells by activation of p21 and downregulation of cyclin D1, cyclin-dependent kinase 4, and phosphorylated Rb. Resveratrol also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. In addition, resveratrol treatment decreased the expression of vascular endothelial growth factor and fibroblast growth factor-2, which might contribute to the inhibition of tumor growth on the bladder cancer xenograft model. These findings suggest that reveratrol could be an important chemoprevention agent for bladder cancer.


Subject(s)
Anticarcinogenic Agents/pharmacology , Apoptosis/drug effects , Stilbenes/pharmacology , Urinary Bladder Neoplasms/drug therapy , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , G1 Phase/drug effects , Humans , Male , Mice , Mice, Inbred BALB C , Resveratrol , Urinary Bladder Neoplasms/pathology , Xenograft Model Antitumor Assays , p38 Mitogen-Activated Protein Kinases/metabolism
3.
Cancer Lett ; 265(2): 206-14, 2008 Jul 08.
Article in English | MEDLINE | ID: mdl-18358601

ABSTRACT

Very recent studies have reported that chemically synthesized small duplex RNAs complementary to the promoters of target genes can activate gene expression in different cancer cell lines. Such dsRNA have been referred to as saRNA for small activating RNA. The present study was conducted to evaluate the potential of p21(WAF1/Cip1) (p21) induction by small activating RNA targeting the p21 promoter in the treatment of bladder cancer. Using T24 human bladder cancer cells, we found that p21 saRNA caused dose- and time-dependent inhibition of cell proliferation and viability which was associated with induced G1-phase cell cycle arrest and apoptosis. The decreased anti-apoptotic protein Bcl-xL and activation of caspase-3 and PARP also supported the efficacy of the treatment. These data suggest that up-regulation of p21 by saRNA may be an effective way for treating human bladder and other types of cancers.


Subject(s)
G1 Phase , Oncogene Protein p21(ras)/metabolism , RNA, Double-Stranded/pharmacology , Up-Regulation , Urinary Bladder Neoplasms/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cell Survival , Humans , Urinary Bladder Neoplasms/drug therapy
4.
Zhonghua Nan Ke Xue ; 13(1): 33-6, 2007 Jan.
Article in Chinese | MEDLINE | ID: mdl-17302032

ABSTRACT

OBJECTIVE: To define the differences in the risk factors for clinical benign prostatic hyperplasia (BPH) between the Mongolian and the Han people. METHODS: Between January 2003 and June 2005, 63 Mongolian and 63 Han patients with BPH were interviewed using a questionnaire consisting of the risk factors for BPH. RESULTS: The intake of alcohol and dairy products was higher in the Mongolians than in the Hans (P <0.05). The consumption of milk tea, dairy products and meat was significantly greater in the Mongolians ( >250 g per day) than in the Hans (P <0.01). And there were more smokers (the smoking index >300) with moderate to severe symptoms (IPSS > 7) in the Mongolians than in the Hans (85.71% vs 57. 14%, P <0.01). The incidence of intraprostatic chronic inflammation and calcification within the prostate gland was higher in the Mongolians (28% vs 11% , P < 0.05; 36.5% vs 15.87% , P < 0.01, respectively). No significant difference was observed between the two groups in body mass, blood pressure, marriage age, offspring number, physical activity, IPSS score and PSA level. CONCLUSION: Compared with Han BPH patients, the Mongolian BPH patients had greater alcohol intake, higher protein diet and higher incidence of intraprostatic chronic inflammation, and those with the smoking index greater than 300 were more likely to receive surgical treatment.


Subject(s)
Prostatic Hyperplasia/epidemiology , Aged , Alcohol Drinking/epidemiology , Asian People , China/epidemiology , Feeding Behavior , Humans , Male , Middle Aged , Risk Factors , Smoking/epidemiology , Surveys and Questionnaires
5.
Biochem Biophys Res Commun ; 354(4): 852-7, 2007 Mar 23.
Article in English | MEDLINE | ID: mdl-17266926

ABSTRACT

Bladder cancer is the fourth most common cancer in men and ninth most common in women. It has a protracted course of progression and is thus an ideal candidate for chemoprevention strategies and trials. This study was conducted to evaluate the chemopreventive/antiproliferative potential of (-)-epigallocatechin gallate (EGCG, the major phytochemical in green tea) against bladder cancer and its mechanism of action. Using the T24 human bladder cancer cell line, we found that EGCG treatment caused dose- and time-dependent inhibition of cellular proliferation and cell viability, and induced apoptosis. Mechanistically, EGCG inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that EGCG may be an important chemoprevention agent for the management of bladder cancer.


Subject(s)
Apoptosis/drug effects , Catechin/analogs & derivatives , Phosphatidylinositol 3-Kinases/physiology , Proto-Oncogene Proteins c-akt/physiology , Proto-Oncogene Proteins c-bcl-2/physiology , Catechin/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , Phosphoinositide-3 Kinase Inhibitors , Urinary Bladder Neoplasms
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