Irinotecan Induces Cell Cycle Arrest, but Not Apoptosis or Necrosis, in Caco-2 and CW2 Colorectal Cancer Cell Lines

被引:14
作者
Kaku, Yoshiko [1 ]
Tsuchiya, Ayako [1 ]
Kanno, Takeshi [1 ]
Nishizaki, Tomoyuki [1 ]
机构
[1] Hyogo Coll Med, Dept Physiol, Div Bioinformat, Nishinomiya, Hyogo 6638501, Japan
关键词
Irinotecan; Anticancer drug; Colorectal cancer; Cell cycle arrest; ORGANIC ANION TRANSPORTER; CPT-11; 7-ETHYL-10-HYDROXYCAMPTOTHECIN; INHIBITION; ACTIVATION; KINASES; SN-38; P53;
D O I
10.1159/000381029
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Irinotecan, a topoisomerase I inhibitor, is clinically used as an anticancer drug. The present study investigated the anticancer effect of irinotecan on p53-negative Caco-2 and p53-positive CW2 human colorectal cancer cell lines. Cell viability for both Caco-2 and CW2 cells was little affected by treatment with irinotecan at concentrations ranging from 0.3 to 30 mu mnol/l for 24-48 h. Irinotecan did not increase the number of TUNEL-positive cells and did not affect the population of propidium iodide (PO-positive and an nexin V-negative cells, corresponding to primary necrosis, or that of PI-positive and annexin-positive cells, corresponding to late apoptosis/secondary necrosis, in either of the two cell lines. In the cell cycle analysis, irinotecan significantly increased the proportions at the S and G(2)/M phases of cell cycling in parallel with a decreased population at the G(1) phase in both cell lines. Irinotecan significantly inhibited tumor growth in mice inoculated with CW2 cells. Taken together, these results indicate that irinotecan induces cell cycle arrest, but not apoptosis or necrosis, both in Caco-2 and CW2 cells, leading to suppression of cell proliferation. (C) 2015 S. Karger AG, Basel
引用
收藏
页码:154 / 159
页数:6
相关论文
共 24 条
[1]   Current status of pharmacological treatment of colorectal cancer [J].
Akhtar, Reyhan ;
Chandel, Shammy ;
Sarotra, Pooja ;
Medhi, Bikash .
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2014, 6 (06) :177-183
[2]   The history and future of targeting cyclin-dependent kinases in cancer therapy [J].
Asghar, Uzma ;
Witkiewicz, Agnieszka K. ;
Turner, Nicholas C. ;
Knudsen, Erik S. .
NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (02) :130-146
[3]   Structural insights into CPT-11 activation by mammalian carboxylesterases [J].
Bencharit, S ;
Morton, CL ;
Howard-Williams, EL ;
Danks, MK ;
Potter, PM ;
Redinbo, MR .
NATURE STRUCTURAL BIOLOGY, 2002, 9 (05) :337-342
[4]   Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth [J].
Bhonde, MR ;
Hanski, ML ;
Notter, M ;
Gillissen, BF ;
Daniel, PT ;
Zeitz, M ;
Hanski, C .
ONCOGENE, 2006, 25 (02) :165-175
[5]  
Chen ZS, 1999, MOL PHARMACOL, V55, P921
[6]  
Chu XY, 1997, J PHARMACOL EXP THER, V281, P304
[7]   The structural mechanisms that underpin mitotic kinase activation [J].
Dodson, Charlotte A. ;
Haq, Tamanna ;
Yeoh, Sharon ;
Fry, Andrew M. ;
Bayliss, Richard .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2013, 41 :1037-1041
[8]   Cell cycle regulation by the NEK family of protein kinases [J].
Fry, Andrew M. ;
O'Regan, Laura ;
Sabir, Sarah R. ;
Bayliss, Richard .
JOURNAL OF CELL SCIENCE, 2012, 125 (19) :4423-4433
[9]  
Haaz MC, 1998, CANCER RES, V58, P468
[10]   Human liver UDP-glucuronosyltransferase isoforms involved in the glucuronidation of 7-ethyl-10-hydroxycamptothecin [J].
Hanioka, N ;
Ozawa, S ;
Jinno, H ;
Ando, M ;
Saito, Y ;
Sawada, J .
XENOBIOTICA, 2001, 31 (10) :687-699