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Open AccessArticle

Induction of G2/M Cell Cycle Arrest and Apoptosis by Genistein in Human Bladder Cancer T24 Cells through Inhibition of the ROS-Dependent PI3k/Akt Signal Transduction Pathway

1
Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan 47340, Korea
2
Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Korea
3
Anti-Aging Research Center, Dong-eui University, Busan 47340, Korea
4
Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea
5
Freshwater Bioresources Utilization Bureau, Nakdonggang National Institute of Biological Resources, Sangju 37242, Korea
6
National Marine Biodiversity Institute of Korea, Seocheon 33662, Korea
7
Department of System Management, Korea Lift College, Geochang 50141, Korea
8
School of Pharmaceutical Sciences, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Henan 450001, China
9
Department of Marine Life Sciences, Jeju National University, Jeju 63243, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Antioxidants 2019, 8(9), 327; https://doi.org/10.3390/antiox8090327
Received: 10 July 2019 / Revised: 8 August 2019 / Accepted: 19 August 2019 / Published: 21 August 2019
(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)
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. View Full-Text
Keywords: genistein; G2/M arrest; apoptosis; ROS; PI3K/Akt genistein; G2/M arrest; apoptosis; ROS; PI3K/Akt
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Park, C.; Cha, H.-J.; Lee, H.; Hwang-Bo, H.; Ji, S.Y.; Kim, M.Y.; Hong, S.H.; Jeong, J.-W.; Han, M.H.; Choi, S.H.; Jin, C.-Y.; Kim, G.-Y.; Choi, Y.H. Induction of G2/M Cell Cycle Arrest and Apoptosis by Genistein in Human Bladder Cancer T24 Cells through Inhibition of the ROS-Dependent PI3k/Akt Signal Transduction Pathway. Antioxidants 2019, 8, 327.

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