Clarification of the molecular pathway of Taiwan local pomegranate fruit juice underlying the inhibition of urinary bladder urothelial carcinoma cell by proteomics strategy.

Li-Ting Hsu,Li-Chien Huang,Bo-Xian Tsang,Li-Yi Chen,Wan-Yin Shih,Ting-Feng Wu

doi:10.1186/s12906-016-1071-7

Abstract

BackgroundPomegranate fruit has been shown to exhibit the inhibitory activity against prostate cancer and lung cancer in vitro and in vivo, which might be a resource for chemoprevention and chemotherapy of cancer. Our previous documented findings indicated that treatment of urinary bladder urothelial carcinoma cell with the ethanol extract isolated from the juice of pomegranate fruit grown in Taiwan could inhibit tumor cell. In this study we intended to uncover the molecular pathway underlying anti-cancer efficacy of Taiwan pomegranate fruit juice against urinary bladder urothelial carcinoma.MethodsWe exploited two-dimensional gel electrophoresis coupled with tandem mass spectrometry to find the de-regulated proteins. Western immunoblotting was used to confirm the results collected from proteomics study.ResultsComparative proteomics indicated that 20 proteins were differentially expressed in ethanol extract-treated T24 cells with 19 up-regulated and 1 down-regulated proteins. These de-regulated proteins were involved in apoptosis, cytoskeleton regulation, cell proliferation, proteasome activity and aerobic glycolysis. Further studies on signaling pathway demonstrated that ethanol extract treatment might inhibit urinary bladder urothelial carcinoma cell proliferation through restriction of PTEN/AKT/mTORC1 pathway via profilin 1 up-regulation. It also might evoke cell apoptosis through Diablo over-expression.ConclusionsThe results of this study provide a global picture to further investigate the anticancer molecular mechanism of pomegranate fruit.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1071-7) contains supplementary material, which is available to authorized users.

Highlights

Pomegranate fruit has been shown to exhibit the inhibitory activity against prostate cancer and lung cancer in vitro and in vivo, which might be a resource for chemoprevention and chemotherapy of cancer
Ellagitannin-rich pomegranate fruit extract (PFE) purified from pomegranate edible portion with 70 % acetone was found to have the apoptotic effects on human lung cancer A549 cells through the down-regulation of cell cycle-regulatory proteins operative in the G1 stage and inhibiting NF-κB as well as MAP kinase pathways [p38, phosphoinositide 3 kinase (PI3K)/ protein kinase B (Akt), c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (Erk)] [6]
Inhibitory impacts of Preparation of ethanol extract (PEE) on outgrowth and migration of urinary bladder urothelial carcinoma (UBUC) cell Our previous documented data demonstrated that PEE might initiate a cascade of biochemical events to induce UBUC cell apoptosis

Summary

Introduction

Pomegranate fruit has been shown to exhibit the inhibitory activity against prostate cancer and lung cancer in vitro and in vivo, which might be a resource for chemoprevention and chemotherapy of cancer. Our previous documented findings indicated that treatment of urinary bladder urothelial carcinoma cell with the ethanol extract isolated from the juice of pomegranate fruit grown in Taiwan could inhibit tumor cell. In this study we intended to uncover the molecular pathway underlying anti-cancer efficacy of Taiwan pomegranate fruit juice against urinary bladder urothelial carcinoma. Our previous documented results showed that pomegranate juice could evoke prostate cancer cell apoptosis via mitochondrial pathway and death receptor signaling. It can interfere with the expression levels of genes involved in cytoskeletal functions, anti-apoptosis, metabolism, NF-B signaling in juice-treated prostate cancer cell [12]

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Results

Conclusion