Cyclin-dependent kinase inhibitors block proliferation of human gastric cancer cells

被引:43
作者
Iseki, H [1 ]
Ko, TC [1 ]
Xue, XY [1 ]
Seapan, A [1 ]
Hellmich, MR [1 ]
Townsend, CM [1 ]
机构
[1] UNIV TEXAS, MED BRANCH, DEPT SURG, GALVESTON, TX 77555 USA
关键词
D O I
10.1016/S0039-6060(97)90008-8
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Olomoucine and rescovitine are novel compounds that are designed to inhibit cyclin-dependent kinases (e.g., Cdk2 and cdc2). Cdks regulate progression through hey checkpoints of the cell cycle. The purpose of this study was to determine (1) whether olomoucine and roscovitine inhibit Cdk2 and cdc2 kinase activities of the human gastric cancer cell line SIIA and (2) whether olomoucine and roscovitine block cell proliferation and cell cycle progression. Methods. SIIA cells were treated with olomoucine or roscovitine a-ltd examined for Cdk2 and cdc2 activities by using histone H1 as the substrate. Cell numbers were counted with a Coulter counter. Cell cycle distribution was analyzed by DNA flow cytometry. Results. Olomoucine and roscovitine completely blocked Cdk2 and cdc2 activities in SIIA cells. Both completely were also able to inhibit proliferation of SIIA cells, as well as three other human gastric cancer cell lines (AGS, MKN45-630, and SNU-1). Cell cycle analysis showed that treatment with olomoucine or roscovitine for 24 hours led to a decrease in the S phase population and an increase in the G2/M population. Conclusions. We have shown that Cdk inhibitors, olomoucine and roscovitine, are a new class of antineoplastic molecules with potential therapeutic benefits for gastric cancers.
引用
收藏
页码:187 / 194
页数:8
相关论文
共 21 条
[1]   CELLULAR EFFECTS OF OLOMOUCINE, AN INHIBITOR OF CYCLIN-DEPENDENT KINASES [J].
ABRAHAM, RT ;
ACQUARONE, M ;
ANDERSEN, A ;
ASENSI, A ;
BELLE, R ;
BERGER, F ;
BERGOUNIOUX, C ;
BRUNN, G ;
BUQUETFAGOT, C ;
FAGOT, D ;
GLAB, N ;
GOUDEAU, H ;
GOUDEAU, M ;
GUERRIER, P ;
HOUGHTON, P ;
HENDRIKS, H ;
KLOAREG, B ;
LIPPAI, M ;
MARIE, D ;
MARO, B ;
MEIJER, L ;
MESTER, J ;
MULNERLORILLON, O ;
POULET, SA ;
SCHIERENBERG, E ;
SCHUTTE, B ;
VAULOT, D ;
VERLHAC, MH .
BIOLOGY OF THE CELL, 1995, 83 (2-3) :105-120
[2]   Inhibition of cell growth by transforming growth factor beta 1 is associated with p53-independent induction of p21 in gastric carcinoma cells [J].
Akagi, M ;
Yasui, W ;
Akama, Y ;
Yokozaki, H ;
Tahara, H ;
Haruma, K ;
Kajiyama, G ;
Tahara, E .
JAPANESE JOURNAL OF CANCER RESEARCH, 1996, 87 (04) :377-384
[3]   FREQUENT AMPLIFICATION OF THE CYCLIN-E GENE IN HUMAN GASTRIC CARCINOMAS [J].
AKAMA, Y ;
YASUI, W ;
YOKOZAKI, H ;
KUNIYASU, H ;
KITAHARA, K ;
ISHIKAWA, T ;
TAHARA, E .
JAPANESE JOURNAL OF CANCER RESEARCH, 1995, 86 (07) :617-621
[4]  
BARRANCO SC, 1991, INVEST NEW DRUG, V9, P29
[5]  
BARRANCO SC, 1983, CANCER RES, V43, P1703
[6]   ASSOCIATION OF HUMAN CYCLIN-E WITH A PERIODIC G(1)-S PHASE PROTEIN-KINASE [J].
DULIC, V ;
LEES, E ;
REED, SI .
SCIENCE, 1992, 257 (5078) :1958-1961
[7]   Cell cycle protein suppression and p21 induction in differentiating Caco-2 cells [J].
Evers, BM ;
Ko, TC ;
Li, J ;
Thompson, EA .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1996, 271 (04) :G722-G727
[8]   OLOMOUCINE, AN INHIBITOR OF THE CDC2/CDK2 KINASES ACTIVITY, BLOCKS PLANT-CELLS AT THE G1 TO S AND G2 TO M CELL-CYCLE TRANSITIONS [J].
GLAB, N ;
LABIDI, B ;
QIN, LX ;
TREHIN, C ;
BERGOUNIOUX, C ;
MEIJER, L .
FEBS LETTERS, 1994, 353 (02) :207-211
[9]   Chemical inhibitors of cyclin-dependent kinases [J].
Meijer, L .
TRENDS IN CELL BIOLOGY, 1996, 6 (10) :393-397
[10]   PRINCIPLES OF CDK REGULATION [J].
MORGAN, DO .
NATURE, 1995, 374 (6518) :131-134