Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway

We examined the anti-cancer effect of genistein, a soy-derived isoflavone, in human bladder transitional cell carcinoma T24 cells. According to our data, genistein induced G2/M phase arrest of the cell cycle and apoptosis. Genistein down-regulated the levels of cyclin A and cyclin B1, but up-regulated the levels of p21WAF1/CIP1, cyclin-dependent kinase (Cdk) inhibitor, that was complexed with Cdc2 and Cdk2. Furthermore, genistein induced the activation of caspases (caspase-3, -8 and -9), and cleavage of poly (ADP-ribose) polymerase cleavage. However, genistein-induced apoptosis was significantly inhibited by a pan-caspase inhibitor, indicating that the induction of apoptosis by genestein was caspase-dependent. In addition, genistein increased the cytosolic release of cytochrome c by increasing the Bax/Bcl-2 ratio and destroying mitochondria integrity. Moreover, genistein inactivated the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, while LY294002, a PI3K/Akt inhibitor, increased the apoptosis-inducing effect of genistein. Genistein further increased the accumulation of reactive oxygen species (ROS), which was significantly suppressed by N-acetyl cysteine (NAC), a ROS scavenger, and in particular, NAC prevented genistein-mediated inactivation of PI3K/Akt signaling, G2/M arrest and apoptosis. Therefore, the present results indicated that genistein promoted apoptosis induction in human bladder cancer T24 cells, which was associated with G2/M phase cell cycle arrest via regulation of ROS-dependent PI3K/Akt signaling pathway.

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β‐Caryophyllene induces apoptosis and inhibits cell proliferation by deregulation of STAT‐3/mTOR/AKT signaling in human bladder cancer cells: An in vitro study

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22863 ◽

2021 ◽

Author(s):

Xiaodong Yu ◽

Bo Liao ◽

Pingyu Zhu ◽

Shulin Cheng ◽

Zhongbo Du ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cancer Cells ◽

In Vitro Study ◽

Akt Signaling ◽

Human Bladder Cancer ◽

Human Bladder ◽

Bladder Cancer Cells ◽

Human Bladder Cancer Cells

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Alterations in the extracellular catabolism of nucleotides are involved in the antiproliferative effect of quercetin in human bladder cancer T24 cells

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2011.10.009 ◽

2013 ◽

Vol 31 (7) ◽

pp. 1204-1211 ◽

Cited By ~ 20

Author(s):

Liliana Rockenbach ◽

Luci Bavaresco ◽

Patrícia Fernandes Farias ◽

Angélica Regina Cappellari ◽

Carlos Henrique Barrios ◽

...

Keyword(s):

Bladder Cancer ◽

Antiproliferative Effect ◽

Human Bladder Cancer ◽

Human Bladder ◽

T24 Cells

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Chemosensitizing effect of maitake mushroom extract on carmustine cytotoxicity in human bladder cancer cells

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20203544 ◽

2020 ◽

Vol 8 (9) ◽

pp. 3154

Author(s):

Joel Hillelsohn ◽

Michael Stern ◽

Mina Iskander ◽

Muhammad Choudhury ◽

Sensuke Konno

Keyword(s):

Oxidative Stress ◽

Bladder Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Anticancer Drugs ◽

Therapeutic Option ◽

Human Bladder Cancer ◽

Human Bladder ◽

Mushroom Extract ◽

T24 Cells

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.

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

BioMed Research International ◽

10.1155/2013/474272 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 20

Author(s):

Xuan Yuan ◽

Defang Li ◽

Hong Zhao ◽

Jiangtao Jiang ◽

Penglong Wang ◽

...

Keyword(s):

Bladder Cancer ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Parp Cleavage ◽

Ros Generation ◽

Human Bladder Cancer ◽

Human Bladder ◽

Licochalcone A ◽

T24 Cells ◽

Stress Dependent

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.

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