Anticancer effect of quinacrine on diffuse large B-cell lymphoma via inhibition of MSI2-NUMB signaling pathway

被引:10
作者
Yang, Shujun [1 ]
Sheng, Lixia [1 ]
Xu, Kaihong [1 ]
Wang, Yi [1 ]
Zhu, Huiling [1 ]
Zhang, Ping [1 ]
Mu, Qitian [1 ]
Ouyang, Guifang [1 ]
机构
[1] Ningbo First Hosp, Dept Hematol, 59 Liuting St, Ningbo 315010, Zhejiang, Peoples R China
关键词
diffuse large B-cell lymphoma; quinacrine; RNA-binding protein Musashi homolog 2-protein numb homolog signaling pathway; apoptosis; cell cycle; RNA-BINDING PROTEIN; NF-KAPPA-B; BREAST-CANCER CELLS; HEPATOCELLULAR-CARCINOMA; SMALL MOLECULES; DNA-BINDING; C-MYC; EXPRESSION; APOPTOSIS; NUMB;
D O I
10.3892/mmr.2017.7892
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma. Despite improvements in the clinical outcomes of DLBCL, similar to 30% of patients will develop relapse/refractory disease. Therefore, novel therapeutic drugs have been investigated to improve disease outcomes. Previous studies have revealed the anticancer effects of quinacrine (QC) on tumor cells in vitro, although its role in human DLBCL is yet to be identified. The present study sought to examine the cytotoxic effect of QC on DLBCL cells. QC induced G0/G1 cell cycle arrest and apoptosis in the DLBCL cell lines SU-DHL-8 and OCI-LY01, in a dose-dependent manner, in addition to the downregulation of cyclin-dependent kinase 4/6 and the upregulation of cleaved poly-ADP ribose polymerase 1. Upon exposure to QC, RNA-binding protein Musashi homolog 2 inactivation and activation of protein numb homolog were observed. In addition, QC was able to inhibit the expression of Myc proto-oncogene protein. The results of the present study indicated that QC may be a potential anti-DLBCL drug.
引用
收藏
页码:522 / 530
页数:9
相关论文
共 39 条
[11]   Control of daughter cell fates during asymmetric division: Interaction of numb and notch [J].
Guo, M ;
Jan, LY ;
Jan, YN .
NEURON, 1996, 17 (01) :27-41
[12]  
Gurova K, 2009, FUTURE ONCOL, V5, P1685, DOI [10.2217/fon.09.127, 10.2217/FON.09.127]
[13]   Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-κB-dependent mechanism of p53 suppression in tumors [J].
Gurova, KV ;
Hill, JE ;
Guo, CH ;
Prokvolit, A ;
Burdelya, LG ;
Samoylova, E ;
Khodyakova, AV ;
Ganapathi, R ;
Ganapathi, M ;
Tararova, ND ;
Bosykh, D ;
Lvovskiy, D ;
Webb, TR ;
Stark, GR ;
Gudkov, AV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (48) :17448-17453
[14]   Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin [J].
Han, Yixiang ;
Ye, Aifang ;
Zhang, Yan ;
Cai, Zhimin ;
Wang, Wei ;
Sun, Lan ;
Jiang, Songfu ;
Wu, Jianbo ;
Yu, Kang ;
Zhang, Shenghui .
PLOS ONE, 2015, 10 (08)
[15]   The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA [J].
Imai, T ;
Tokunaga, A ;
Yoshida, T ;
Hashimoto, M ;
Mikoshiba, K ;
Weinmaster, G ;
Nakafuku, M ;
Okano, H .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (12) :3888-3900
[16]   Inhibition of NF-κB Signaling by Quinacrine Is Cytotoxic to Human Colon Carcinoma Cell Lines and Is Synergistic in Combination with Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) or Oxaliplatin [J].
Jani, Tanvi S. ;
DeVecchio, Jennifer ;
Mazumdar, Tapati ;
Agyeman, Akwasi ;
Houghton, Janet A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (25) :19162-19172
[17]   Overexpression of Numb suppresses growth, migration, and invasion of human clear cell renal cell carcinoma cells [J].
Jin Sima ;
Zhang, Bao ;
Yu, Yuanzi ;
Sima, Xinyuan ;
Mao, Yanxin .
TUMOR BIOLOGY, 2015, 36 (04) :2885-2892
[18]   Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP [J].
Kawahara, Hironori ;
Imai, Takao ;
Imataka, Hiroaki ;
Tsujimoto, Masafumi ;
Matsumoto, Ken ;
Okano, Hideyuki .
JOURNAL OF CELL BIOLOGY, 2008, 181 (04) :639-653
[19]  
Kong DS, 2008, ONCOL REP, V19, P639
[20]   Alternative splicing of the cell fate determinant Numb in hepatocellular carcinoma [J].
Lu, Yinying ;
Xu, Wanping ;
Ji, Junfang ;
Feng, Dechun ;
Sourbier, Carole ;
Yang, Youfeng ;
Qu, Jianhui ;
Zeng, Zhen ;
Wang, Chunping ;
Chang, Xiujuan ;
Chen, Yan ;
Mishra, Alok ;
Xu, Max ;
Lee, Min-Jung ;
Lee, Sunmin ;
Trepel, Jane ;
Linehan, W. Marston ;
Wang, Xinwei ;
Yang, Yongping ;
Neckers, Len .
HEPATOLOGY, 2015, 62 (04) :1122-1131