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Nutrients 2018, 10(5), 543; https://doi.org/10.3390/nu10050543

Deciphering the Molecular Mechanism Underlying the Inhibitory Efficacy of Taiwanese Local Pomegranate Peels against Urinary Bladder Urothelial Carcinoma

1
Department of Medical Research, Chi Mei Medical Center, Tainan 710, Taiwan
2
Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan
3
Department of Pathology, Chi Mei Medical Center, Tainan 710, Taiwan
*
Author to whom correspondence should be addressed.
Received: 3 April 2018 / Revised: 21 April 2018 / Accepted: 24 April 2018 / Published: 27 April 2018
(This article belongs to the Special Issue Natural Products for Cancer Prevention and Therapy)
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Abstract

Pomegranate (Punica granatum L.) fruit has been demonstrated to have the inhibitory activities to various tumors. In this study, we try to uncover the molecular mechanism underlying the inhibitory capability of Taiwanese local pomegranate fruit to urinary bladder urothelial carcinoma. The results collected from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated that the ethanol extract of pomegranate peel exhibited better inhibitory activity to human urinary bladder urothelial carcinoma T24 and J82 cells than that of pulp. Furthermore, the ethylacetate layer of peel ethanol extract was observed to have the best inhibitory activity against urinary bladder urothelial carcinoma cells. One of the eight fractions (PEPE2 fraction) collected from the ethylacetate layer with Diaion HP-20 column chromatography demonstrated the highest inhibitory activity in urinary bladder urothelial carcinoma cells. The results of the flow cytometry and apoptotic pathway studies suggested that the inhibitory activity of PEPE2 fraction were attributed to the UBUC cell apoptosis. To confirm the above results, our results of xenograft-induced bladder tumor in nude mice showed that the oral consumption of the ethylacetate layer (2, 5, 10 and 100 mg/kg) could decrease the volume and weight of T24 tumors and caused the apoptosis in the xenografted tumors, which was observed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. This study provided the likelihood that the traditionally non-edible pomegranate peel waste is re-utilized to make an affordable and promising chemopreventive product to prevent UBUC incidence or recurrence. View Full-Text
Keywords: apoptosis; T24 cells; death receptor pathway; mitochondrial pathway; endoplasmic reticulum stress; pomegranate peel; urinary bladder urothelial carcinoma apoptosis; T24 cells; death receptor pathway; mitochondrial pathway; endoplasmic reticulum stress; pomegranate peel; urinary bladder urothelial carcinoma
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Chang, C.-P.; Chan, Y.-Y.; Li, C.-F.; Chien, L.-H.; Lee, S.-T.; Wu, T.-F. Deciphering the Molecular Mechanism Underlying the Inhibitory Efficacy of Taiwanese Local Pomegranate Peels against Urinary Bladder Urothelial Carcinoma. Nutrients 2018, 10, 543.

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