Cellular response and activation of apoptosis by mithramycin SK in p21WAF1-deficient HCT116 human colon carcinoma cells

被引：11

作者：

Bataller, Marc ^{[1
]}

Mendez, Carmen ^{[2
]}

Salas, Jose A. ^{[2
]}

Portugal, Jose ^{[1
]}

机构：

[1] CSIC, Inst Biol Mol Barcelona, E-08028 Barcelona, Spain

[2] Univ Oviedo, Inst Univ Oncol Principado Asturias, Dept Biol Funct, Oviedo, Spain

来源：

CANCER LETTERS | 2010年 / 292卷 / 01期

关键词：

HCT116; cells; p21(WAF1); Apoptosis; Cell death; Caspase; 2; PRODUCER STREPTOMYCES-ARGILLACEUS; MITOTIC CATASTROPHE; GENE-EXPRESSION; ANTITUMOR DRUG; CDK INHIBITORS; DNA-DAMAGE; P53; CANCER; BINDING; ARREST;

D O I：

10.1016/j.canlet.2009.11.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

HCT116 (p21(-/-)) human colon carcinoma cells treated with mithramycin SK (MSK), a novel analog of the antitumor antibiotic mithramycin A (MTA), were transiently arrested in G2/M, with some cells entering a faulty mitotic cycle without cytokinesis that resulted in G1-like cell arrest, which consisted of post-mitotic aneuploid Cl cells. Some of these cells synthesized DNA and elicited an apoptotic response. The absence of p21(WAF1) made HCT116 cells more sensitive to MSK than to the related MTA. MSK also showed higher anti-proliferative activity than MTA on HCT116 cells with different genetic backgrounds, including those lacking the p53 gene. Apoptosis in MSK-treated p21(-/-) cells involved caspase 2 rather than caspase 3. Untreated HCT116 (p21(-/-)) cells presented a little caspase 3 activity, which increased slightly after treatment with MSK. The apoptotic response in p21(-/-) cells comprised caspase 2 acting as an executor caspase together with a loss of mitochondrial membrane potential that may be initiated by caspase 2. In contrast, caspase 3 was activated in wild-type HCT116 after treatment with MSK. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：80 / 90

页数：11

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