scholarly journals Licochalcone A-Induced Human Bladder Cancer T24 Cells Apoptosis Triggered by Mitochondria Dysfunction and Endoplasmic Reticulum Stress

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Xuan Yuan ◽  
Defang Li ◽  
Hong Zhao ◽  
Jiangtao Jiang ◽  
Penglong Wang ◽  
...  

Licochalcone A (LCA), a licorice chalconoid, is considered to be a bioactive agent with chemopreventive potential. This study investigated the mechanisms involved in LCA-induced apoptosis in human bladder cancer T24 cells. LCA significantly inhibited cells proliferation, increased reactive oxygen species (ROS) levels, and caused T24 cells apoptosis. Moreover, LCA induced mitochondrial dysfunction, caspase-3 activation, and poly-ADP-ribose polymerase (PARP) cleavage, which displayed features of mitochondria-dependent apoptotic signals. Besides, exposure of T24 cells to LCA triggered endoplasmic reticulum (ER) stress; as indicated by the enhancement in 78 kDa glucose-regulated protein (GRP 78), growth arrest and DNA damage-inducible gene 153/C/EBP homology protein (GADD153/CHOP) expression, ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12. All the findings from our study suggest that LCA initiates mitochondrial ROS generation and induces oxidative stress that consequently causes T24 cell apoptosis via the mitochondria-dependent and the ER stress-triggered signaling pathways.

2013 ◽  
Vol 25 (1) ◽  
pp. 206-213 ◽  
Author(s):  
Qing-you Zheng ◽  
Ping-ping Li ◽  
Feng-suo Jin ◽  
Chen Yao ◽  
Guo-hui Zhang ◽  
...  

2013 ◽  
Vol 31 (7) ◽  
pp. 1204-1211 ◽  
Author(s):  
Liliana Rockenbach ◽  
Luci Bavaresco ◽  
Patrícia Fernandes Farias ◽  
Angélica Regina Cappellari ◽  
Carlos Henrique Barrios ◽  
...  

Author(s):  
Joel Hillelsohn ◽  
Michael Stern ◽  
Mina Iskander ◽  
Muhammad Choudhury ◽  
Sensuke Konno

Background: Despite several therapeutic options available for bladder cancer, the outcomes are less satisfactory.  To find a more effective modality, we were interested in the bioactive mushroom extract, PDF, which has been shown to sensitize certain anticancer drugs.  Accordingly, we investigated if cytotoxic effects of several anticancer drugs used on bladder cancer patients could be enhanced with PDF in vitro.Methods: Human bladder cancer T24 cells were treated with four anticancer drugs, carmustine (BCNU), 5-fluorouracil (5FU), cisplatin (CPL), and doxorubicin (DOX) alone, their combinations, or in combination with PDF, and cell viability was determined.  To explore the anticancer mechanism, the status of glyoxalase I (Gly-I), an enzyme involved in the drug resistance of cancer cells, and oxidative stress that can cause severe cellular injury/damage was also assessed.Results: BCNU and 5FU alone resulted in a >50% reduction in cell viability but CPL and DOX had no such effects.  Only a combination of BCNU and PDF led to a drastic (~90%) cell viability reduction, accompanied by inactivation of Gly-I and an increase in oxidative stress.  However, any combinations of other drugs and PDF had little effects on cell viability, Gly-I activity, or severity of oxidative stress.Conclusions: This study shows that anticancer activity of BCNU is significantly potentiated with PDF in T24 cells.  This is rather attributed to inactivated Gly-I and increased oxidative stress.  Therefore, PDF appears to have a chemosensitizing effect capable of enhancing BCNU cytotoxicity, which may offer an alternative, improved therapeutic option for bladder cancer.


Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2881 ◽  
Author(s):  
Yih-Gang Goan ◽  
Wen-Tung Wu ◽  
Chih-I Liu ◽  
Choo-Aun Neoh ◽  
Yu-Jen Wu

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.


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

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.


2019 ◽  
Vol 13 (4) ◽  
pp. 324-333 ◽  
Author(s):  
Sung Ok Kim ◽  
Hee-Jae Cha ◽  
Cheol Park ◽  
Hyesook Lee ◽  
Su Hyun Hong ◽  
...  

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