Ellagic acid induces apoptosis in tsgh8301 human bladder cancer cells through the endoplasmic reticulum stress- and mitochondria-dependent signaling pathways

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Chin-Chih Ho ◽  
An-Cheng Huang ◽  
Chun-Shu Yu ◽  
Jin-Cherng Lien ◽  
Shin-Hwar Wu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Ellagic Acid ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Bladder Cancer Cells ◽  
Human Bladder Cancer Cells

scholarly journals Involvement of Mitochondrial Dysfunction, Endoplasmic Reticulum Stress, and the PI3K/AKT/mTOR Pathway in Nobiletin-Induced Apoptosis of Human Bladder Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2881 ◽  
Author(s):  
Yih-Gang Goan ◽  
Wen-Tung Wu ◽  
Chih-I Liu ◽  
Choo-Aun Neoh ◽  
Yu-Jen Wu
Keyword(s):  
Bladder Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Bladder Cancer Cells ◽  
Induced Apoptosis ◽  
Human Bladder Cancer Cells

Nobiletin (NOB) is a polymethoxylated flavonoid isolated from citrus fruit peel that has been shown to possess anti-tumor, antithrombotic, antifungal, anti-inflammatory and anti-atherosclerotic activities. The main purpose of this study was to explore the potential of using NOB to induce apoptosis in human bladder cancer cells and study the underlying mechanism. Using an MTT assay, agarose gel electrophoresis, a wound-healing assay, flow cytometry, and western blot analysis, this study investigated the signaling pathways involved in NOB-induced apoptosis in BFTC human bladder cancer cells. Our results showed that NOB at concentrations of 60, 80, and 100 μM inhibited cell growth by 42%, 62%, and 80%, respectively. Cells treated with 60 μM NOB demonstrated increased DNA fragmentation, and flow cytometry analysis confirmed that the treatment caused late apoptotic cell death. Western blot analysis showed that mitochondrial dysfunction occurred in NOB-treated BFTC cells, leading to cytochrome C release into cytosol, activation of pro-apoptotic proteins (caspase-3, caspase-9, Bad, and Bax), and inhibition of anti-apoptotic proteins (Mcl-1, Bcl-xl, and Bcl-2). NOB-induced apoptosis was also mediated by regulating endoplasmic reticulum stress via the PERK/elF2α/ATF4/CHOP pathway, and downregulating the PI3K/AKT/mTOR pathway. Our results suggested that the cytotoxic and apoptotic effects of NOB on bladder cancer cells are associated with endoplasmic reticulum stress and mitochondrial dysfunction.

scholarly journals Flaccidoxide-13-Acetate-Induced Apoptosis in Human Bladder Cancer Cells is through Activation of p38/JNK, Mitochondrial Dysfunction, and Endoplasmic Reticulum Stress Regulated Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (5) ◽  
pp. 287 ◽  
Author(s):  
Yu-Jen Wu ◽  
Tzu-Rong Su ◽  
Guo-Fong Dai ◽  
Jui-Hsin Su ◽  
Chih-I Liu
Keyword(s):  
Flow Cytometry ◽  
Bladder Cancer ◽  
Endoplasmic Reticulum ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Bladder Cancer Cells ◽  
Induced Apoptosis ◽  
Human Bladder Cancer Cells

Flaccidoxide-13-acetate, an active compound isolated from cultured-type soft coral Sinularia gibberosa, has been shown to have inhibitory effects against invasion and cell migration of RT4 and T24 human bladder cancer cells. In our study, we used an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation assay, and flow cytometry to determine the mechanisms of the anti-tumor effect of flaccidoxide-13-acetate. The MTT and colony formation assays showed that the cytotoxic effect of flaccidoxide-13-acetate on T24 and RT4 cells was dose-dependent, and the number of colonies formed in the culture was reduced with increasing flaccidoxide-13-acetate concentration. Flow cytometry analysis revealed that flaccidoxide-13-acetate induced late apoptotic events in both cell lines. Additionally, we found that flaccidoxide-13-acetate treatment upregulated the expressions of cleaved caspase 3, cleaved caspase 9, Bax, and Bad, and down-regulated the expressions of Bcl-2, p-Bad, Bcl-x1, and Mcl-1. The results indicated that apoptotic events were mediated by mitochondrial dysfunction via the caspase-dependent pathway. Flaccidoxide-13-acetate also provoked endoplasmic reticulum (ER) stress and led to activation of the PERK-eIF2α-ATF6-CHOP pathway. Moreover, we examined the PI3K/AKT signal pathway, and found that the expressions of phosphorylated PI3K (p-PI3K) and AKT (p-AKT) were decreased with flaccidoxide-13-acetate concentrations. On the other hand, our results showed that the phosphorylated JNK and p38 were obviously activated. The results support the idea that flaccidoxide-13-acetate-induced apoptosis is mediated by mitochondrial dysfunction, ER stress, and activation of both the p38 and JNK pathways, and also relies on inhibition of PI3K/AKT signaling. These findings imply that flaccidoxide-13-acetate has potential in the development of chemotherapeutic agents for human bladder cancer.

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