Induction of the cell cycle arrest and apoptosis by flavonoids isolated from Korean Citrus aurantium L. in non-small-cell lung cancer cells

被引:49
作者
Park, Kwang Il [1 ,2 ]
Park, Hyeon Soo [1 ,2 ]
Nagappan, Arulkumar [1 ,2 ]
Hong, Gyeong Eun [1 ,2 ]
Lee, Do Hoon [1 ,2 ]
Kang, Sang Rim [3 ]
Kim, Jin A. [4 ,5 ]
Zhang, Jue
Kim, Eun Hee [6 ]
Lee, Won Sup [7 ]
Shin, Sung Chul [8 ,9 ]
Hah, Young Sool [10 ]
Kim, Gon Sup [1 ,2 ]
机构
[1] Gyeongsang Natl Univ, Life Sci Res Inst, Gazwa 660701, Jinju, South Korea
[2] Gyeongsang Natl Univ, Coll Vet Med, Gazwa 660701, Jinju, South Korea
[3] Kyonggi Univ, Sch Nat Sci, Dept Biol Engn, Suwon 443760, South Korea
[4] Gyeongsang Natl Univ, Korea Natl Anim Res Resource Ctr, Gazwa 660701, Jinju, South Korea
[5] Gyeongsang Natl Univ, Korea Natl Anim Bioresource Bank, Gazwa 660701, Jinju, South Korea
[6] Int Univ Korea, Dept Nursing Sci, Jinju 660759, South Korea
[7] Gyeongsang Natl Univ, Gyeongsang Natl Univ Hosp, Sch Med,Dept Internal Med, Inst Hlth Sci,Gyeongnam Reg Canc Ctr, Jinju 660702, South Korea
[8] Gyeongsang Natl Univ, Dept Chem, Jinju 660701, South Korea
[9] Gyeongsang Natl Univ, Life Sci Res Inst, Jinju 660701, South Korea
[10] Gyeongsang Natl Univ Hosp, Clin Res Inst, Jinju 660702, South Korea
基金
新加坡国家研究基金会;
关键词
Korean Citrus aurantium L; Flavonoid; Human lung cancer cells; Cell cycle arrest; Apoptosis; BCL-2 FAMILY PROTEINS; HUMAN COLON-CANCER; MAMMALIAN-CELLS; PHOSPHORYLATION; KINASE; TRANSITIONS; ACTIVATION; REGULATORS; PATHWAY; DEATH;
D O I
10.1016/j.foodchem.2012.06.097
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
This study investigated the anti-proliferative and apoptotic effect of flavonoids isolated from Korean Citrus aurantium L using A549 lung cancer cells. Flavonoids potently inhibited of A549 cells in a dose-dependent manner, whereas flavonoids had a weak inhibitory effect on proliferation of WI-38 cells. Flow cytometry and Western blot analysis showed that flavonoids induced cell cycle arrest at the G2/M check-point by controlling the proteins expression level of cyclin B1, cdc2, cdc25c and p21(WAF1/CIP1). Also, flavonoids induced apoptosis through the regulation of the expression of caspases, cleaved PARP and Bax/Bcl-xL ratio. The activity of caspase-3 on A549 cells increased in a dose-dependent manner. These results clearly indicated that the anti-cancer effect of flavonoids on A549 cells follows multiple cellular pathways through G2/M arrest and the induction of apoptosis. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2728 / 2735
页数:8
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