5-allyl-7-gen-difluoromethoxychrysin enhances TRAIL-induced apoptosis in human lung carcinoma A549 cells

BMC Cancer

Research Article

Zhao-Hui Xie¹  Fei Liu²  Jian-Song Zhang²  Jian-Guo Cao²  Mei-Fang Quan² 

[1] Changsha Health Vocational College, 410010, Changsha, Hunan Province, China;Medical College, Hunan Normal University, 410013, Changsha, Hunan Province, China;Medical College, Hunan Normal University, 410013, Changsha, Hunan Province, China;

关键词: Lung cancer;    chrysin;    5-allyl-7-gen-difluoromethoxychrysin;    TRAIL;    apoptosis;    therapeutic action;   

DOI  :  10.1186/1471-2407-11-322

 received in 2010-12-24, accepted in 2011-07-29,  发布年份 2011

来源: Springer

【 摘 要 】

Background5-allyl-7-gen-difluoromethoxychrysin (AFMC) is a novel synthetic analogue of chrysin that has been reported to inhibit proliferation in various cancer cell lines. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent.MethodsThe cytotoxicity of A549 and WI-38 cells were determined using colorimetry. Apoptosis was detected by flow cytometry (FCM) after propidium iodide (PI) fluorescence staining and agarose gel electrophoresis. Caspase activities were evaluated using enzyme-linked immunosorbent assay (ELISA).The expressions of DR4 and DR5 were analyzed using FCM and western blot.ResultsSubtoxic concentrations of AFMC sensitize human non-small cell lung cancer (NSCLC) A549 cells to TRAIL-mediated apoptosis. Combined treatment of A549 cells with AFMC and TRAIL significantly activated caspase-3, -8 and -9. The caspase-3 inhibitor zDEVD-fmk and the caspase-8 inhibitor zIETD-fmk blocked the apoptosis of A549 cells induced by co-treatment with AFMC and TRAIL. In addition, we found that treatment of A549 cells with AFMC significantly induced the expression of death receptor 5 (DR5). AFMC-mediated sensitization of A549 cells to TRAIL was efficiently reduced by administration of a blocking antibody or small interfering RNAs against DR5. AFMC also caused increase of the Sub-G1 cells by TRAIL treatment and increased the expression levels of DR5 in other NSCLC H460 and H157 cell lines. In contrast, AFMC-mediated induction of DR5 expression was not observed in human embryo lung WI-38 cells, and AFMC did not sensitize WI-38 cells to TRAIL-induced apoptosis.ConclusionsAFMC synergistically enhances TRAIL-mediated apoptosis in NSCLC cells through up-regulating DR5 expression.

【 授权许可】

Unknown   
© Xie et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.