Suppression of growth of A549 lung cancer cells by waltonitone and its mechanisms of action

被引:15
作者
Zhang, Yi [1 ]
Zhang, Guo-Bin [2 ]
Xu, Xiao-Man [3 ]
Zhang, Meng [1 ]
Qu, Dan [3 ]
Niu, Hui-Yan [1 ]
Bai, Xue [1 ]
Kan, Liang [1 ]
He, Ping [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Geriatr, Shenyang 110004, Peoples R China
[2] Shenyang Ctr Dis Control & Prevent, Shenyang 110004, Peoples R China
[3] China Med Univ, Shengjing Hosp, Dept Resp Med, Shenyang 110004, Peoples R China
关键词
waltonitone; miRNAs; lung cancer A549 cells; apoptosis; IN-VITRO; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; PANCREATIC-CANCER; DOWN-REGULATION; APOPTOSIS; PROGNOSIS; PATHWAY; PROLIFERATION; CHEMOTHERAPY;
D O I
10.3892/or.2012.1869
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Natural compounds are a great source of cancer chemotherapeutic agents. Our investigation indicates that waltonitone, a triterpene extracted from medicinal plants, inhibits the proliferation of A549 cells in a concentration- and time-dependent manner. Waltonitone induced apoptosis of A549 cells in a concentration-dependent manner, as determined by fluorescence microscopy and flow cytometry. The apoptosis was accompanied by increased Bax protein levels and decreased Bcl-2 protein levels in A549 cells. Furthermore, the treatment of A549 cells with waltonitone altered the expression of miRNAs. We found that 27 miRNAs were differentially expressed in waltonitone-treated cells, of which 8 miRNAs target genes related to cell proliferation and apoptosis. In summary, our results demonstrate that waltonitone has a significant inhibitory effect on the proliferation of A549 cells. It is possible that upregulation of Bax/Bcl-2 and regulation of expression of specific miRNAs play a role in inhibition of proliferation and induction of apoptosis in waltonitone-treated cells. Waltonitone can be applied to lung carcinoma as a chemotherapeutic candidate.
引用
收藏
页码:1029 / 1035
页数:7
相关论文
共 36 条
[1]   MicroRNA pathways in flies and worms: Growth, death, fat, stress, and timing [J].
Ambros, V .
CELL, 2003, 113 (06) :673-676
[2]   The regulation of genes and genomes by small RNAs [J].
Ambros, Victor ;
Chen, Xuemei .
DEVELOPMENT, 2007, 134 (09) :1635-1641
[3]   The new World Health Organization classification of lung tumours [J].
Brambilla, E ;
Travis, WD ;
Colby, TV ;
Corrin, B ;
Shimosato, Y .
EUROPEAN RESPIRATORY JOURNAL, 2001, 18 (06) :1059-1068
[4]   Regulation of apoptosis by Bcl-2 family proteins [J].
Burlacu, A .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2003, 7 (03) :249-257
[5]   Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].
Calin, GA ;
Dumitru, CD ;
Shimizu, M ;
Bichi, R ;
Zupo, S ;
Noch, E ;
Aldler, H ;
Rattan, S ;
Keating, M ;
Rai, K ;
Rassenti, L ;
Kipps, T ;
Negrini, M ;
Bullrich, F ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529
[6]   Postresectional adjuvant intraportal chemotherapy in patients with hepatocellular carcinoma: A case-control study [J].
Chau, Gar-Yang ;
Lui, Wing-Yiu ;
Tsay, Shyh-Haw ;
Chao, Yee ;
King, Kuang-Liang ;
Wu, Chew-Wun .
ANNALS OF SURGICAL ONCOLOGY, 2006, 13 (10) :1329-1337
[7]   MicroRNAs as oncogenes and tumor suppressors [J].
Chen, CZ .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1768-1771
[8]   International comparisons of survival from lung cancer: pitfalls and warnings [J].
Erridge, Sara C. ;
Moller, Henrik ;
Price, Allan ;
Brewster, David .
NATURE CLINICAL PRACTICE ONCOLOGY, 2007, 4 (10) :570-577
[9]   Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer [J].
Harikumar, Kuzhuvelil B. ;
Kunnumakkara, Ajaikumar B. ;
Sethi, Gautam ;
Diagaradjane, Parmeswaran ;
Anand, Preetha ;
Pandey, Manoj K. ;
Gelovani, Juri ;
Krishnan, Sunil ;
Guha, Sushovan ;
Aggarwal, Bharat B. .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (02) :257-268
[10]   Molecular origins of cancer: Lung cancer [J].
Herbst, Roy S. ;
Heymach, John V. ;
Lippman, Scott M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (13) :1367-1380