scholarly journals Induction of Apoptosis by Costunolide in Bladder Cancer Cells is Mediated through ROS Generation and Mitochondrial Dysfunction

Molecules ◽  
2013 ◽  
Vol 18 (2) ◽  
pp. 1418-1433 ◽  
Author(s):  
Azhar Rasul ◽  
Rui Bao ◽  
Mahadev Malhi ◽  
Bing Zhao ◽  
Ichiro Tsuji ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Ros Generation ◽  
Bladder Cancer Cells ◽  
Induction Of Apoptosis

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 Proteomics Analysis of Tangeretin-Induced Apoptosis through Mitochondrial Dysfunction in Bladder Cancer Cells

2019 ◽  
Vol 20 (5) ◽  
pp. 1017 ◽  
Author(s):  
Jen-Jie Lin ◽  
Chun-Chieh Huang ◽  
Yu-Li Su ◽  
Hao-Lun Luo ◽  
Nai-Lun Lee ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Differentially Expressed ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Citrus Peel ◽  
Bladder Cancer Cells ◽  
Induced Apoptosis ◽  
Human Bladder Cancer Cells

Tangeretin is one of the most abundant compounds in citrus peel, and studies have shown that it possesses anti-oxidant and anti-cancer properties. However, no study has been conducted on bladder cancer cells. Bladder cancer has the second highest mortality rate among urological cancers and is the fifth most common malignancy in the world. Currently, combination chemotherapy is the most common approach by which to treat patients with bladder cancer, and thus identifying more effective chemotherapeutic agents that can be safely administered to patients is a very important research issue. Therefore, this study investigated whether tangeretin can induce apoptosis and identified the signaling pathways of tangeretin-induced apoptosis in human bladder cancer cells using two-dimensional gel electrophoresis (2DGE). The results of the study demonstrated that 60 μM tangeretin reduced the cell survival of a BFTC-905 bladder carcinoma cell line by 42%, and induced early and late apoptosis in the cells. In this study 2DGE proteomics technology identified 41 proteins that were differentially-expressed in tangeretin-treated cells, and subsequently LC–MS/MS analysis was performed to identify the proteins. Based on the functions of the differentially-expressed proteins, the results suggested that tangeretin caused mitochondrial dysfunction and further induced apoptosis in bladder cancer cells. Moreover, western blotting analysis demonstrated that tangeretin treatment disturbed calcium homeostasis in the mitochondria, triggered cytochrome C release, and activated caspase-3 and caspase-9, which led to apoptosis. In conclusion, our results showed that tangeretin-induced apoptosis in human bladder cancer cells is mediated by mitochondrial inactivation, suggesting that tangeretin has the potential to be developed as a new drug for the treatment of bladder cancer.

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.

Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members

2015 ◽  
Vol 29 (10) ◽  
pp. 1516-1524 ◽  
Author(s):  
Jin-Woo Jeong ◽  
Won Sup Lee ◽  
Se-il Go ◽  
Arulkumar Nagappan ◽  
Jun Young Baek ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Family Members ◽  
Ros Generation ◽  
Pachymic Acid ◽  
Bladder Cancer Cells

Induction of Apoptosis of Cytokine-Producing Bladder Cancer Cells by Adenovirus-Mediated I kappa B alpha Overexpression

1999 ◽  
Vol 10 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Makoto Sumitomo ◽  
Masaaki Tachibana ◽  
Masaru Murai ◽  
Masamichi Hayakawa ◽  
Hiroshi Nakamura ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
I Kappa B Alpha ◽  
Bladder Cancer Cells ◽  
Induction Of Apoptosis

scholarly journals Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells

2014 ◽  
Vol 33 (2) ◽  
pp. 566-572 ◽  
Author(s):  
SYED MINHAJ UDDIN AHMED ◽  
XIUXIAN WU ◽  
XINGHUA JIN ◽  
XIA ZHANG ◽  
YOSHIKAZU TOGO ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Bladder Cancer Cells ◽  
Synergistic Induction ◽  
Induction Of Apoptosis ◽  
Human Bladder Cancer Cells

scholarly journals BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

2010 ◽  
Vol 10 (1) ◽  
pp. 21 ◽  
Author(s):  
Katja Schwarzer ◽  
Martin Foerster ◽  
Thomas Steiner ◽  
Inge-Marie Hermann ◽  
Eberhard Straube
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Bladder Cancer Cells ◽  
Induction Of Apoptosis
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