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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

Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan 47340, Korea
Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Korea
Anti-Aging Research Center, Dong-eui University, Busan 47340, Korea
Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, Korea
Freshwater Bioresources Utilization Bureau, Nakdonggang National Institute of Biological Resources, Sangju 37242, Korea
National Marine Biodiversity Institute of Korea, Seocheon 33662, Korea
Department of System Management, Korea Lift College, Geochang 50141, Korea
School of Pharmaceutical Sciences, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Henan 450001, China
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;
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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