Flavopiridol, an inhibitor of transcription - Implications, problems and solutions

被引：108

作者：

Blagosklonny, MV ^{[1
]}

机构：

[1] New York Med Coll, Brander Canc Res Inst, Hawthorne, NY 10532 USA

来源：

CELL CYCLE | 2004年 / 3卷 / 12期

关键词：

flavopiridol; chemotherapy; cancer; CDK; transcription; p53;

D O I：

10.4161/cc.3.12.1278

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

After a decade of exciting promises, the CDK inhibitor flavopiridol has quietly failed in most clinical trials. This review discusses that flavopiridol is a potent inhibitor of global transcription. This explains not only downregulation of numerous proteins, cell cycle arrest and apoptosis but also all pleiotropic and mysterious effects of flavopiridol. Yet, flavopiridol is not just a second actinomycin D. As an inhibitor of transcription with a unique mechanism of action, flavopiridol may have tremendous clinical potentials. This article reviews the molecular and cellular effects of flavopiridol as well as mechanisms of therapeutic and side effects, suggesting its novel clinical applications as a single agent and in drug combinations.

引用

页码：1537 / 1542

页数：6

共 100 条

[1] Phase II study of flavopiridol in patients with advanced colorectal cancer
Aklilu, M
Kindler, HL
Donehower, RC
Mani, S
Vokes, EE
[J]. ANNALS OF ONCOLOGY, 2003, 14 (08) : 1270 - 1273
[2] Aleem E, 2004, CELL CYCLE, V3, P35
[3] Alonso M, 2003, MOL CANCER THER, V2, P139
[4] Protease inhibitor-induced apoptosis:: accumulation of wt p53, p21WAF1/CIP1 and induction of apoptosis are independent markers of proteasome inhibition
An, WG
Hwang, SG
Trepel, JB
Blagosklonny, MV
[J]. LEUKEMIA, 2000, 14 (07) : 1276 - 1283
[5] Inhibitors of transcription, proteasome inhibitors, and DNA-damaging drugs differentially affect feedback of p53 degradation
An, WG
Chuman, Y
Fojo, T
Blagosklonny, MV
[J]. EXPERIMENTAL CELL RESEARCH, 1998, 244 (01) : 54 - 60
[6] Transcription abnormalities potentiate apoptosis of normal human fibroblasts
Andera, L
Wasylyk, B
[J]. MOLECULAR MEDICINE, 1997, 3 (12) : 852 - 863
[7] Arguello F, 1998, BLOOD, V91, P2482
[8] Bible KC, 1996, CANCER RES, V56, P4856
[9] Flavopiridol downregulates the expression of both the inducible NO synthase and p27kip1 in malignant cells from B-cell chronic lymphocytic leukemia
Billard, C
Kern, C
Tang, R
Ajchenbaum-Cymbalista, F
Kolb, JP
[J]. LEUKEMIA, 2003, 17 (12) : 2435 - 2443
[10] Cyclotherapy Protection of Normal Cells and Unshielding of Cancer Cells
Blagosklonny, Mikhail V.
Darzynkiewicz, Zbigniew
[J]. CELL CYCLE, 2002, 1 (06) : 375 - 382

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