Morusin inhibits cell proliferation and tumor growth by down-regulating c-Myc in human gastric cancer

被引:41
作者
Wang, Feng [1 ]
Zhang, Dunke [1 ]
Mao, Jingxin [1 ]
Ke, Xiao-Xue [1 ]
Zhang, Rui [1 ]
Yin, Chao [1 ]
Gao, Ning [2 ]
Cui, Hongjuan [1 ]
机构
[1] Southwest Univ, State Key Lab Silkworm Genome Biol, Chongqing, Peoples R China
[2] Third Mil Med Univ, Coll Pharm, Dept Pharmacognosy, Chongqing, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
morusin; c-Myc; cell proliferation; tumor growth; gastric cancer; NF-KAPPA-B; IN-VITRO; CHALCONE DERIVATIVES; CYCLIN D1; EXPRESSION; SUPPRESSES; APOPTOSIS; GENE; BAICALEIN; VIVO;
D O I
10.18632/oncotarget.19231
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Morusin is a pure extract from the root bark of Morus australis (Moraceae). In recent years, morusin has been reported to exhibit anti-tumor biological activity in some types of human cancers through different mechanisms. Here, we attempted to investigate the inhibitory effect and mechanism of morusin on gastric cancer. Morusin markedly inhibited gastric cancer cell proliferation by down-regulating CDKs and Cyclins, such as CDK2, CDK4, Cyclin D1 and Cyclin E1. Additionally, morusin suppressed tumor growth in vitro and in vivo. Up-regulation of CDKs and Cyclins in gastric cancer cells was induced by c-Myc binding at the E-Box regions of CDKs and the Cyclin promoter. In addition, compared with the control group, the morusin-treated group showed reduced expression of c-Myc and c-Myc protein binding at the E-Box regions. Based on these results, we overexpressed c-Myc in gastric cancer cells and found that overexpressing c-Myc rescued morusin-induced inhibition of cell proliferation and tumor growth. These results suggest that morusin inhibits cell proliferation and tumor growth by down-regulating c-Myc in human gastric cancer.
引用
收藏
页码:57187 / 57200
页数:14
相关论文
共 41 条
[1]   Myc and cell cycle control [J].
Bretones, Gabriel ;
Dolores Delgado, M. ;
Leon, Javier .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2015, 1849 (05) :506-516
[2]   Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo [J].
Cathcart, Mary-Clare ;
Useckaite, Zivile ;
Drakeford, Clive ;
Semik, Vikki ;
Lysaght, Joanne ;
Gately, Kathy ;
O'Byrne, Kenneth J. ;
Pidgeon, Graham P. .
BMC CANCER, 2016, 16
[3]   Baicalein induces apoptosis via ROS-dependent activation of caspases in human bladder cancer 5637 cells [J].
Choi, Eun-Ok ;
Park, Cheol ;
Hwang, Hye-Jin ;
Hong, Su Hyun ;
Kim, Gi-Young ;
Cho, Eun-Ju ;
Kim, Wun-Jae ;
Choi, Yung Hyun .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2016, 49 (03) :1009-1018
[4]  
DAKSIS JI, 1994, ONCOGENE, V9, P3635
[5]   Roles of Kruppel-like factor 4 in normal homeostasis, cancer and stem cells [J].
Evans, Paul M. ;
Liu, Chunming .
ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2008, 40 (07) :554-564
[6]   Anticancer activity of flavane gallates isolated from Plicosepalus curviflorus [J].
Fawzy, Ghada Ahmed ;
Al-Taweel, Areej Mohammad ;
Perveen, Shagufta .
PHARMACOGNOSY MAGAZINE, 2014, 10 (39) :519-523
[7]   Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 [J].
Ferlay, Jacques ;
Shin, Hai-Rim ;
Bray, Freddie ;
Forman, David ;
Mathers, Colin ;
Parkin, Donald Maxwell .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (12) :2893-2917
[8]   Induction of KLF4 in basal keratinocytes blocks the proliferation - differentiation switch and initiates squamous epithelial dysplasia [J].
Foster, KW ;
Liu, ZL ;
Nail, CD ;
Li, XN ;
Fitzgerald, TJ ;
Bailey, SK ;
Frost, AR ;
Louro, ID ;
Townes, TM ;
Paterson, AJ ;
Kudlow, JE ;
Lobo-Ruppert, SM ;
Ruppert, JM .
ONCOGENE, 2005, 24 (09) :1491-1500
[9]   Antinephritis and radical scavenging activity of prenylflavonoids [J].
Fukai, T ;
Satoh, K ;
Nomura, T ;
Sakagami, H .
FITOTERAPIA, 2003, 74 (7-8) :720-724
[10]   Morusin Inhibits Glioblastoma Stem Cell Growth In Vitro and In Vivo Through Stemness Attenuation, Adipocyte Transdifferentiation, and Apoptosis Induction [J].
Guo, Huijie ;
Liu, Chuanlan ;
Yang, Liuqi ;
Dong, Lihua ;
Wang, Li ;
Wang, Qiaoping ;
Li, Haiyan ;
Zhang, Jie ;
Lin, Ping ;
Wang, Xiujie .
MOLECULAR CARCINOGENESIS, 2016, 55 (01) :77-89