Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450

被引:61
作者
Chen, Ping [1 ,2 ]
Zhang, Jing-Yang [1 ,2 ]
Sha, Bei-Bei [1 ,2 ]
Ma, Yan-Er [1 ,2 ]
Hu, Tao [1 ,2 ]
Ma, Yang-Cheng [1 ,2 ]
Sun, Hao [3 ]
Shi, Jian-Xiang [3 ]
Dong, Zi-Ming [1 ,2 ]
Li, Pei [1 ,2 ]
机构
[1] Zhengzhou Univ, Canc Chemoprevent Collaborat Innovat Ctr Henan Pr, Zhengzhou 450001, Henan, Peoples R China
[2] Zhengzhou Univ, Coll Basic Med Sci, Dept Pathophysiol, Zhengzhou 450001, Henan, Peoples R China
[3] Zhengzhou Univ, Affiliated Tumor Hosp, Coll Publ Hlth, Henan Key Lab Tumor Epidemiol, Zhengzhou 450001, Henan, Peoples R China
关键词
luteolin; esophageal squamous carcinoma; cell proliferation; mitochondrial membrane potential; chemotherapy; CYCLIN-DEPENDENT KINASES; BREAST-CANCER CELLS; DIETARY FLAVONOIDS; G(2)/M ARREST; TUMOR-GROWTH; G2/M ARREST; DNA-DAMAGE; INDUCTION; GENISTEIN; APIGENIN;
D O I
10.18632/oncotarget.15832
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In current study, we investigated the anti-tumor effect of luteolin in human ESCC cell lines in vitro and in vivo and tried to explore the potential mechanisms. Results from flow cytometry showed that luteolin could induce apoptosis and caspase-3 activation and induce cell cycle arrest at G2/M phase in a dose-and time-dependent manner in EC1 and KYSE450 cells. JC-1 test results showed that membrane potential of mitochondria after luteolin treatment was down-regulated and this was an indicator for intrinsic apoptosis. Western Blot results showed the expression of cell cycle regulatory protein p21 and p53 increased and three apoptosis related proteins that participate in mitochondrial apoptotic pathway, namely, Bim, CYT-c and cPARP, also increased in luteolin treated cells compared with control groups. We further confirmed that luteolin could significantly inhibit the growth of ESCC tumors in xenograft mouse models and no evidence of systemic toxicity was observed. Our results suggest that luteolin can induce cell apoptosis and cell cycle arrest in G2/M phase through mitochondrial pathway in EC1 and KYSE450 cell lines and proper utilization of luteolin might be a practical approach in ESCC chemotherapy.
引用
收藏
页码:27471 / 27480
页数:10
相关论文
共 55 条
[1]   Neoadjuvant or Adjuvant Therapy for Resectable Esophageal Cancer: Is There a Standard of Care? [J].
Almhanna, Khaldoun ;
Shridhar, Ravi ;
Meredith, Kenneth L. .
CANCER CONTROL, 2013, 20 (02) :89-96
[2]   Luteolin Arrests Cell Cycling, Induces Apoptosis and Inhibits the JAK/STAT3 Pathway in Human Cholangiocarcinoma Cells [J].
Aneknan, Ploypailin ;
Kukongviriyapan, Veerapol ;
Prawan, Auemduan ;
Kongpetch, Sarinya ;
Sripa, Banchob ;
Senggunprai, Laddawan .
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 2014, 15 (12) :5071-5076
[3]   Neoadjuvant, surgery and adjuvant chemotherapy without radiation for esophageal cancer [J].
Ardalan, Bach ;
Spector, Seth A. ;
Livingstone, Alan S. ;
Franceschi, Dido ;
Mezentsev, Dmitry ;
Lima, Mayra ;
Bowen-Wells, Carol P. ;
Sparling, Lynne ;
Avisar, Eli ;
Sapp, Michelle ;
Rios, Joyce ;
Walker, Gail ;
Ganjei-Azar, Parvin .
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 2007, 37 (08) :590-596
[4]   Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals [J].
Cai, QY ;
Rahn, RO ;
Zhang, RW .
CANCER LETTERS, 1997, 119 (01) :99-107
[5]   Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1 [J].
Casagrande, F ;
Darbon, JM .
BIOCHEMICAL PHARMACOLOGY, 2001, 61 (10) :1205-1215
[6]   A prospective phase II trial of S-1 and cisplatin-based chemoradiotherapy for locoregionally advanced esophageal cancer [J].
Chang, Hyun ;
Shin, Sung Kwan ;
Cho, Byoung Chul ;
Lee, Chang-Geol ;
Kim, Choong Bai ;
Kim, Dae Joon ;
Lee, Jin Gu ;
Hur, Jin ;
Lee, Chang Young ;
Bae, Mi Kyung ;
Kim, Hye Ryun ;
Lee, Sang Kil ;
Park, Jun Chul ;
Lee, Hyuk ;
Kim, Hyoung-Il ;
Chung, Hyunsoo ;
Cha, Jihye ;
Lee, Yong Chan ;
Kim, Joo-Hang .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2014, 73 (04) :665-671
[7]   Increase of Bax/Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line [J].
Chang, JS ;
Hsu, YL ;
Kuo, PL ;
Kuo, YC ;
Chiang, LC ;
Lin, CC .
LIFE SCIENCES, 2005, 76 (16) :1883-1893
[8]   Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo [J].
Chian, Song ;
Thapa, Ruby ;
Chi, Zhexu ;
Wang, Xiu Jun ;
Tang, Xiuwen .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 447 (04) :602-608
[9]   Concurrent chemoradiotherapy with S-1 and cisplatin in advanced esophageal cancer [J].
Cho, S. -H. ;
Shim, H. -J. ;
Lee, S. R. ;
Ahn, J. -S. ;
Yang, D. -H. ;
Kim, Y. -K. ;
Nam, T. K. ;
Lee, J. -J. ;
Kim, H. -J. ;
Chung, I. -J. .
DISEASES OF THE ESOPHAGUS, 2008, 21 (08) :697-703
[10]  
Choi JA, 2001, INT J ONCOL, V19, P837