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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 109105, 14 pages
Research Article

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

1Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan
2Department of Pharmacology, School of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan
3Department of Education and Research, Taichung Veterans General Hospital, Taichung 407, Taiwan
4Center for General Education, Tunghai University, Taichung 407, Taiwan
5Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan
6Graduate School of Nursing, Hung-Kuang University, Taichung 433, Taiwan

Received 26 August 2012; Revised 23 December 2012; Accepted 2 January 2013

Academic Editor: Hong Q. Zhang

Copyright © 2013 Yen-Chuan Ou et al. 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.


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.