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Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells

There is a growing interest in the health-promoting effects of natural substances obtained from plants. Although luteolin has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity, the molecular mechanisms have not been well elu...

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Autores principales: Ou, Yen-Chuan, Kuan, Yu-Hsiang, Li, Jian-Ri, Raung, Shue-Ling, Wang, Chung-Chiang, Hung, Yu-Yeh, Chen, Chun-Jung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576787/
https://www.ncbi.nlm.nih.gov/pubmed/23476679
http://dx.doi.org/10.1155/2013/109105
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author Ou, Yen-Chuan
Kuan, Yu-Hsiang
Li, Jian-Ri
Raung, Shue-Ling
Wang, Chung-Chiang
Hung, Yu-Yeh
Chen, Chun-Jung
author_facet Ou, Yen-Chuan
Kuan, Yu-Hsiang
Li, Jian-Ri
Raung, Shue-Ling
Wang, Chung-Chiang
Hung, Yu-Yeh
Chen, Chun-Jung
author_sort Ou, Yen-Chuan
collection PubMed
description There is a growing interest in the health-promoting effects of natural substances obtained from plants. Although luteolin has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity, the molecular mechanisms have not been well elucidated. This study provides evidence of an alternative target for luteolin and sheds light on the mechanism of its physiological benefits. Treatment of 786-O renal cell carcinoma (RCC) cells (as well as A498 and ACHN) with luteolin caused cell apoptosis and death. This cytotoxicity was caused by the downregulation of Akt and resultant upregulation of apoptosis signal-regulating kinase-1 (Ask1), p38, and c-Jun N-terminal kinase (JNK) activities, probably via protein phosphatase 2A (PP2A) activation. In addition to being a concurrent substrate of caspases and event of cell death, heat shock protein-90 (HSP90) cleavage might also play a role in driving further cellular alterations and cell death, at least in part, involving an Akt-related mechanism. Due to the high expression of HSP90 and Akt-related molecules in RCC and other cancer cells, our findings suggest that PP2A activation might work in concert with HSP90 cleavage to inactivate Akt and lead to a vicious caspase-dependent apoptotic cycle in luteolin-treated 786-O cells.
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spelling pubmed-35767872013-03-09 Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells Ou, Yen-Chuan Kuan, Yu-Hsiang Li, Jian-Ri Raung, Shue-Ling Wang, Chung-Chiang Hung, Yu-Yeh Chen, Chun-Jung Evid Based Complement Alternat Med Research Article There is a growing interest in the health-promoting effects of natural substances obtained from plants. Although luteolin has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity, the molecular mechanisms have not been well elucidated. This study provides evidence of an alternative target for luteolin and sheds light on the mechanism of its physiological benefits. Treatment of 786-O renal cell carcinoma (RCC) cells (as well as A498 and ACHN) with luteolin caused cell apoptosis and death. This cytotoxicity was caused by the downregulation of Akt and resultant upregulation of apoptosis signal-regulating kinase-1 (Ask1), p38, and c-Jun N-terminal kinase (JNK) activities, probably via protein phosphatase 2A (PP2A) activation. In addition to being a concurrent substrate of caspases and event of cell death, heat shock protein-90 (HSP90) cleavage might also play a role in driving further cellular alterations and cell death, at least in part, involving an Akt-related mechanism. Due to the high expression of HSP90 and Akt-related molecules in RCC and other cancer cells, our findings suggest that PP2A activation might work in concert with HSP90 cleavage to inactivate Akt and lead to a vicious caspase-dependent apoptotic cycle in luteolin-treated 786-O cells. Hindawi Publishing Corporation 2013 2013-02-05 /pmc/articles/PMC3576787/ /pubmed/23476679 http://dx.doi.org/10.1155/2013/109105 Text en Copyright © 2013 Yen-Chuan Ou et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ou, Yen-Chuan
Kuan, Yu-Hsiang
Li, Jian-Ri
Raung, Shue-Ling
Wang, Chung-Chiang
Hung, Yu-Yeh
Chen, Chun-Jung
Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells
title Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells
title_full Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells
title_fullStr Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells
title_full_unstemmed Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells
title_short Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells
title_sort induction of apoptosis by luteolin involving akt inactivation in human 786-o renal cell carcinoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576787/
https://www.ncbi.nlm.nih.gov/pubmed/23476679
http://dx.doi.org/10.1155/2013/109105
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