Sulforaphane retards the growth of UM-UC-3 xenographs, induces apoptosis, and reduces survivin in athymic mice

• Published in: Nutrition research (New York, N.Y.) Vol. 32; no. 5; pp. 374 - 380
• Main Authors: Wang, Fengqian, Shan, Yujuan
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2012; Elsevier
• Subjects: Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis - drug effects; Athymic mice; Biological and medical sciences; Bladder cancer; Brassica - chemistry; Caspase 3 - metabolism; Caspase-3; Cell Line, Tumor; Cytochrome c; Cytochromes c - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Humans; Inhibitor of Apoptosis Proteins - metabolism; Isothiocyanates; Male; Mice; Mice, Nude; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Repressor Proteins - metabolism; Sulforaphane; Survivin; Surviving; Thiocyanates - pharmacology; Thiocyanates - therapeutic use; Thymus Gland; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Xenograft Model Antitumor Assays; hematoxylin and eosin; BC; Athymic mice; isothiocyanates; Bladder cancer; Caspase-3; TFA; Cytochrome c; body weight; terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling; trifluoroacetic acid; TUNEL; Surviving; BW; Sulforaphane; high-performance liquid chromatography; ITCs; SFN; HE; HPLC; Urinary system disease; Enzyme; Growth; Cysteine endopeptidases; Rodentia; Caspase; Urinary tract disease; Malignant tumor; Survivin; Peptidases; Vertebrata; Mammalia; Mouse; Animal; Hydrolases; Bladder disease; Cancer; Apoptosis
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2012.03.014

Abstract Sulforaphane (SFN), an isothiocyanate that exists exclusively in cruciferous vegetables, may be the most promising preventive agent for bladder cancer (BC) to date. We previously observed that SFN dramatically inhibits human BC T24 cells in vitro. Our hypothesis is that SFN may attenuate BC growth. To test our hypothesis, we investigated the effect of SFN on human BC UM-UC-3 cell xenografts implanted into athymic mice. Sulforaphane extract was routinely prepared in our laboratory, and its content was measured with high-performance liquid chromatography. Athymic mice were injected subcutaneously with a UM-UC-3 cell suspension (2.0 × 106 cells/200 μ L per mouse) and randomly divided into 2 groups. The positive control group was orally gavaged with water, and the treatment group was orally administered SFN from broccoli sprout (12 mg/kg body weight) for 5 weeks. At the end of the experiment, tumor tissues were harvested and processed for hematoxylin and eosin staining and immunohistochemistry. The average tumor volume decreased from 4.1 ± 1.67 cm3 in the positive control mice to 1.5 ± 0.72 cm3 in the SFN-treated mice, evidencing an inhibitory rate of 63%. The SFN extract also reduced the appearance of tumors, including karyopyknosis and angiogenesis. Sulforaphane extract induced caspase 3 and cytochrome c expression but reduced the expression of survivin. Sulforaphane extract retards the growth of UM-UC-3 xenografts in vivo, confirming its future potential in BC therapy.