Abstract
BackgroundPomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action.MethodsEdible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract.ResultsThis study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell.ConclusionsThe analytical results of this study help to provide insight into the molecular mechanism of induced bladder cancer cell apoptosis by pomegranate and to develop novel mechanism-based chemopreventive strategy for bladder cancer.
Highlights
Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor
Anthocyanin/ ellagitannin-rich pomegranate fruit extract (PFE) prepared from pomegranate edible portion with 70% acetone was found to evoke the apoptotic impacts on human lung cancer A549 cells by hampering NF-κB as well as MAP kinase pathway (p38, PI3K/Akt, JNK and Erk) and the down-regulation of cell cycle-regulatory proteins functioning in the G1 stage [11]
In this study we examine the inhibitory function of pomegranate fruit ethanol extract (PEE) in urinary bladder urothelial carcinoma (UBUC)
Summary
Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. PFE can cause G1-phase arrest of prostate cancer PC3 cell through dwindling the expressions of cyclins D and E and increasing the levels of cyclindependent kinase-2, -4 and -6, and resulting in an increase in WAF1/p21 as well as KIP1/p27 [13]. It provokes PC3 cell apoptosis by over-expression of proapoptotic Bax and Bak while down-regulating anti-apoptotic Bcl-2 as well as Bcl-XL. A phase II clinical study for men with rising PSA after surgery or radiotherapy demonstrated that pomegranate juice can statistically prolong PSA doubling time, suggesting potential preventive efficacy of pomegranate in human prostate cancer [16]
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