期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 56, 期 -, 页码 100-109出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2013.02.022
关键词
Luteolin; Apoptosis; Autophagy; ER stress
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science, and Technology, Republic of Korea [2010-0008843, 2012-0000476]
- National Research Foundation of Korea [2010-0008843] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In this study, we investigated the anti-cancer effects of luteolin, a member of the flavonoid family, in NCI-H460 human lung carcinoma cells. It was shown that luteolin induces apoptotic cell death through modulating both the extrinsic pathway and intrinsic pathways, which are suppressed by z-VAD-fmk, indicating that luteolin triggers caspase-dependant apoptosis. Furthermore, we found that the alpha subunit of the eukaryotic initiation factor 2 (eIF2 alpha/C/EBP homologous protein pathway, but not the c-Jun N-terminal kinase pathway, played a critical role in induction of apoptosis by luteolin. The data indicated that luteolin also induces autophagy; evidence for this is the accumulation of microtubule-associated protein light chain-3 (LC3) II protein, the increase of LC3 puncta as well as an enhanced autophagy flux. In addition, inhibiting autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that luteolin-induced autophagy functions as a cell death mechanism. Notably, the activated caspases that appeared with luteolin treatment cleaved Beclin-1, and the expression of LC3II remained the same even after cells were challenged with Beclin-1 siRNA, demonstrating that luteolin induces Beclin-1-independent autophagy. Taken together, our findings showed that luteolin triggers both endoplasmic reticulum stress-related apoptosis and non-canonical autophagy, which function as a cell death mechanism in NCI-H460 human lung cancer cells. (C) 2013 Elsevier Ltd. All rights reserved.
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