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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

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-regulat...

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Autores principales: Park, Cheol, Cha, Hee-Jae, Lee, Hyesook, Hwang-Bo, Hyun, Ji, Seon Yeong, Kim, Min Yeong, Hong, Su Hyun, Jeong, Jin-Woo, Han, Min Ho, Choi, Sung Hyun, Jin, Cheng-Yun, Kim, Gi-Young, Choi, Yung Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769882/
https://www.ncbi.nlm.nih.gov/pubmed/31438633
http://dx.doi.org/10.3390/antiox8090327
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author Park, Cheol
Cha, Hee-Jae
Lee, Hyesook
Hwang-Bo, Hyun
Ji, Seon Yeong
Kim, Min Yeong
Hong, Su Hyun
Jeong, Jin-Woo
Han, Min Ho
Choi, Sung Hyun
Jin, Cheng-Yun
Kim, Gi-Young
Choi, Yung Hyun
author_facet Park, Cheol
Cha, Hee-Jae
Lee, Hyesook
Hwang-Bo, Hyun
Ji, Seon Yeong
Kim, Min Yeong
Hong, Su Hyun
Jeong, Jin-Woo
Han, Min Ho
Choi, Sung Hyun
Jin, Cheng-Yun
Kim, Gi-Young
Choi, Yung Hyun
author_sort Park, Cheol
collection PubMed
description 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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spelling pubmed-67698822019-10-30 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 Park, Cheol Cha, Hee-Jae Lee, Hyesook Hwang-Bo, Hyun Ji, Seon Yeong Kim, Min Yeong Hong, Su Hyun Jeong, Jin-Woo Han, Min Ho Choi, Sung Hyun Jin, Cheng-Yun Kim, Gi-Young Choi, Yung Hyun Antioxidants (Basel) Article 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. MDPI 2019-08-21 /pmc/articles/PMC6769882/ /pubmed/31438633 http://dx.doi.org/10.3390/antiox8090327 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Cheol
Cha, Hee-Jae
Lee, Hyesook
Hwang-Bo, Hyun
Ji, Seon Yeong
Kim, Min Yeong
Hong, Su Hyun
Jeong, Jin-Woo
Han, Min Ho
Choi, Sung Hyun
Jin, Cheng-Yun
Kim, Gi-Young
Choi, Yung Hyun
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769882/
https://www.ncbi.nlm.nih.gov/pubmed/31438633
http://dx.doi.org/10.3390/antiox8090327
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