Cell death triggered by synthetic flavonoids in human leukemia cells is amplified by the inhibition of extracellular signal-regulated kinase signaling

被引：15
作者：
Rubio, Sara [1 ]
Leon, Francisco [2 ]
Quintana, Jose [1 ]
Cutler, Stephen [3 ,4 ]
Estevez, Francisco [1 ]
机构：
[1] Univ Las Palmas Gran Canaria, Inst Canario Invest Canc, Dept Biochem & Mol Biol, Associated Unit,Spanish Natl Res Council CSIC, Las Palmas Gran Canaria 35016, Spain
[2] Inst Prod Nat & Agrobiol CSIC, Tenerife 38206, Spain
[3] Univ Mississippi, Sch Pharm, Dept Med Chem, University, MS 38677 USA
[4] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷
关键词：
Apoptosis; Caspases; Cell cycle; Cytotoxicity; ACTIVATED PROTEIN-KINASE; INDUCED APOPTOSIS; DIETARY FLAVONOIDS; GROWTH-INHIBITION; CARCINOMA-CELLS; MAPK PATHWAY; QUERCETIN; CANCER; CISPLATIN; CASPASES;
D O I：
10.1016/j.ejmech.2012.07.028
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new class of methyl esters of flavonoids, with different substituents on the B ring were synthesized and evaluated for their antiproliferative activity against the human leukemia cell line HL-60. The presence of either a methyl group (1f) or a chlorine atom (1o) at position 2' of the B ring played an important role in affecting antiproliferative activity. The cytotoxic effects of these compounds were accompanied by the concentration- and time-dependent appearance of DNA- and nuclear-fragmentation, increase in the percentage of sub-G(1) cells, and processing of multiple caspases and poly(ADP-ribose)polymerase cleavage. Pretreatment of cells with the specific mitogen-activated extracellular kinases (MEK) 1/2 inhibitor PD98059, together with if and 1o, resulted in an important enhancement of cell death, which might have clinical implications for the use of both compounds in combination with MEK 1/2 inhibitors as potential therapeutic agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：284 / 296
页数：13
相关论文
共 45 条
[1]   Astragalin heptaacetate-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway [J].
Burmistrova, Olga ;
Quintana, Jose ;
Diaz, Jesus G. ;
Estevez, Francisco .
CANCER LETTERS, 2011, 309 (01) :71-77
[2]   Serine/threonine protein kinases and apoptosis [J].
Cross, TG ;
Scheel-Toellner, D ;
Henriquez, NV ;
Deacon, E ;
Salmon, M ;
Lord, JM .
EXPERIMENTAL CELL RESEARCH, 2000, 256 (01) :34-41
[3]  
CUTLER SJ, 1990, HETEROCYCLES, V31, P651
[4]   SYNTHESIS OF FLAVONE-8-CARBOXYLIC ACID ANALOGS AS POTENTIAL ANTITUMOR AGENTS [J].
CUTLER, SJ ;
ELKABBANI, FM ;
KEANE, C ;
FISHERSHORE, SL ;
MCCABE, FL ;
JOHNSON, RK ;
BLANTON, CD .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1993, 28 (05) :407-414
[5]   Signal transduction by the JNK group of MAP kinases [J].
Davis, RJ .
CELL, 2000, 103 (02) :239-252
[6]   Conditional expression of mitogen-activated protein kinase phosphatase-1, MKP-1, is cytoprotective against UV-induced apoptosis [J].
Franklin, CC ;
Srikanth, S ;
Kraft, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (06) :3014-3019
[7]   Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells [J].
Galan, A ;
Garcia-Bermejo, ML ;
Troyano, A ;
Vilaboa, NE ;
de Blas, E ;
Kazanietz, MG ;
Aller, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (15) :11418-11424
[8]  
HARKER WG, 1989, CANCER RES, V49, P4542
[9]   The biochemistry and medical significance of the flavonoids [J].
Havsteen, BH .
PHARMACOLOGY & THERAPEUTICS, 2002, 96 (2-3) :67-202
[10]   Inhibition of extracellular signal-regulated protein kinase or c-Jun N-terminal protein kinase cascade, differentially activated by cisplatin, sensitizes human ovarian cancer cell line [J].
Hayakawa, J ;
Ohmichi, M ;
Kurachi, H ;
Ikegami, H ;
Kimura, A ;
Matsuoka, T ;
Jikihara, H ;
Mercola, D ;
Murata, Y .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (44) :31648-31654
12345