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• W2020121837 abstract "You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2014MP21-14 UTILIZING DIETARY SUPPLEMENTS TO TARGET BIOMARKERS OF BLADDER CANCER METASTASIS David Alonzo, Travis Yates, Kelly Hoye, and Vinata Lokeshwar David AlonzoDavid Alonzo More articles by this author , Travis YatesTravis Yates More articles by this author , Kelly HoyeKelly Hoye More articles by this author , and Vinata LokeshwarVinata Lokeshwar More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.842AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES HA and HYAL-1 hyaluronidase family molecules are potential markers for Bladder Cancer (BCa) diagnosis and predicting prognosis and promote tumor growth and metastasis. 4-Methylumbelliferone (4-MU) is an orally bioavailable dietary supplement that inhibits HA synthesis. Epithelial mesenchymal transition (EMT) is the hallmark of invasion and metastasis. Since HA promotes tumor metastasis and EMT, we evaluated the expression of EMT markers in bladder tissues and antitumor effects of 4-MU in BCa models. METHODS Quantitative PCR was used to measure mRNA expression of EMT genes (Beta-catenin, Twist, and Snail) in 66 bladder tissue specimens (27 normal; 39 tumor); follow-up: 26 + or - 4.3 months; median 20 months. The effect of 4-MU (40 – 120 μg/ml) on cell proliferation, apoptosis, intracellular signaling, and the expression of HA receptors and EMT genes were examined in BCa cell lines, 253J-Lung and HT1376. Effect of 4-MU on tumor growth was analyzed in subcutaneous xenografts. RESULTS Among the EMT genes, Snail and Twist were differentially expressed in BCa tissues when compared to normal bladder (P<0.001). Furthermore, elevated Twist expression significantly correlated with metastasis (2-fold increase; P=0.028). Beta-catenin expression negatively correlated with survival (chi square=4.3, p=0.038). At IC50 for HA synthesis, 4-MU inhibited proliferation (∼ 2.5-fold) and induced apoptosis (3-fold) in BCa cells. 4-MU induced caspase-8, -9 and -3 activation and up-regulation of Fas and FADD. 4-MU caused 4-10-fold downregulation of HA-receptors (CD44, RHAMM), and EMT promoters - Beta-catenin, Snail and Twist, but increased E-cadherin expression by 2-fold. In xenograft studies, 4-MU significantly decreased tumor growth (> 3-fold) when treatment was started either on the day of tumor cell injection or after tumors became palpable. No weight loss or serum or organ toxicity was observed in treated mice. Tumors showed reduced microvessel density (∼3-fold) and HA expression but increased TURNEL positive cells. CONCLUSIONS This study shows that expression of EMT determinants correlates with clinical outcome. Furthermore, the non-toxic dietary supplement 4-MU has potent antitumor activity and reverses EMT. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e230-e231 Advertisement Copyright & Permissions© 2014MetricsAuthor Information David Alonzo More articles by this author Travis Yates More articles by this author Kelly Hoye More articles by this author Vinata Lokeshwar More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2020121837 title "MP21-14 UTILIZING DIETARY SUPPLEMENTS TO TARGET BIOMARKERS OF BLADDER CANCER METASTASIS" @default.
• W2020121837 doi "https://doi.org/10.1016/j.juro.2014.02.842" @default.
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