N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells

被引：43

作者：

Hsin, I-Lun ^{[1
]}

Sheu, Gwo-Tarng ^{[1
]}

Chen, Hung-Hsuan ^{[1
]}

Chiu, Ling-Yen ^{[1
]}

Wang, Horng-Dar ^{[5
,6
]}

Chan, Hsiu-Wen ^{[1
]}

Hsu, Chung-Ping ^{[3
,4
]}

Ko, Jiunn-Liang ^{[1
,2
]}

机构：

[1] Chung Shan Med Univ, Inst Med & Mol Toxicol, Taichung 40203, Taiwan

[2] Chung Shan Med Univ Hosp, Dept Med Oncol & Chest Med, Taichung, Taiwan

[3] Vet Gen Hosp Taichung, Dept Thorac Surg, Taichung, Taiwan

[4] Taipei Vet Gen Hosp, Taipei, Taiwan

[5] Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu 30013, Taiwan

[6] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu 30013, Taiwan

来源：

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS | 2010年 / 688卷 / 1-2期

关键词：

Curcumin; Telomerase activity; N-acetyl cysteine; Sp1; Reactive oxygen species; HTERT GENE PROMOTER; HEME OXYGENASE-1; C-MYC; DOWN-REGULATION; CYCLE ARREST; CANCER-CELLS; APOPTOSIS; EXPRESSION; ANTIOXIDANT; ACTIVATION;

D O I：

10.1016/j.mrfmmm.2010.03.011

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Curcumin is a natural compound that has been extensively observed due to its potential as an anticancer drug Curcumin restrains cancer cell progression via telomerase activity suppression. However, the exact mechanism is still unknown In this study, we demonstrate that the effects of curcumin on cell viability and telomerase activity can be blunted by reactive oxygen species (ROS) inhibitor N-acetyl cysteine (NAG) The ROS induced by curcumin in A549 cells was detected by flow cytometry. Using Western blot and RTPCR, human telomerase reverse transcriptase (hTERT) decreased in the presence of curcumin. Sp1 is one of the important transcription factors in hTERT expression. Our data showed that curcumin decreases the expression of Sp1 through proteasome pathway. In addition, NAG blunted the Sp1 reduction and hTERT downregulation by curcumin Further, reporter assay and DNA affinity precipitation assay confirmed the influence of curcumin on Sp1 in hTERT regulation This is the first study to demonstrate that curcumin induces ROS production resulting in Sp1 binding activity inhibition and hTERT downregulation (C) 2010 Elsevier B V. All rights reserved

引用

页码：72 / 77

页数：6

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