Cyclin-dependent kinase inhibitor, P276-00 induces apoptosis in multiple myeloma cells by inhibition of Cdk9-T1 and RNA polymerase II-dependent transcription

被引：49

作者：

Manohar, Sonal M. ^{[1
]}

Rathos, Maggie J. ^{[1
]}

Sonawane, Vinay ^{[1
]}

Rao, Shalini V. ^{[1
]}

Joshi, Kalpana S. ^{[1
]}

机构：

[1] Piramal Life Sci Ltd, Dept Pharmacol, Bombay 400063, Maharashtra, India

来源：

LEUKEMIA RESEARCH | 2011年 / 35卷 / 06期

关键词：

P276-00; Multiple myeloma; Cdk9; Mcl-1; DOWN-REGULATION; IN-VIVO; EXPRESSION; MCL-1; SURVIVAL; BCL-2; PROTEIN; DEATH; GENE; SHOWS;

D O I：

10.1016/j.leukres.2010.12.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

P276-00 is a novel cyclin-dependent kinase inhibitor especially potent for Cdk9-T1, Cdk4-D1 and Cdk1-B. Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of malignant plasma cells. Treatment of MM cell lines with P276-00 resulted in apoptosis that correlated with transcription inhibition and a significant decline in Mcl-1 protein levels with the appearance of cleaved PARP in these cells. In vivo studies of P276-00 confirmed antitumor activity in RPMI-8226 xenograft. These results suggest that P276-00 causes multiple myeloma cell death by disrupting the balance between cell survival and apoptosis through inhibition of transcription and downregulation of Mcl-1. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：821 / 830

页数：10

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