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.
Highlights
Bladder cancer is the most common tumor of the urinary system in the world and ranked the9th in male cancer incidence in Taiwan in 2014 [1,2]
We found that the ethanol extract isolated from pomegranate peels (PEP) exhibited a better inhibitory activity comparatively to urinary bladder urothelial carcinoma (UBUC) cells than that of pulps
We found that the ethanol extract isolated from pomegranate peels exhibited a better inhibitory comparatively
Summary
Bladder cancer is the most common tumor of the urinary system in the world and ranked the. 9th in male cancer incidence in Taiwan in 2014 [1,2]. Urothelial carcinoma is the most encountered lesion among various bladder tumor types, which contributes to more than 90% of the bladder cancer cases in developed countries [1]. According to WHO classification (2004), urinary bladder urothelial carcinoma (UBUC) cells can be classified into the low or high grades. Nutrients 2018, 10, 543 local recurrence can be observed in some UBUCs even followed by lethal distal spreading [3]. In terms of disease management, it may be beneficial that a chemopreventive product for bladder cancer can be used by cancer patients or high-risk persons to avoid tumor recurrence or incidence
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