N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells.
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 (NAC). The ROS induced by curcumin in A549 cells was detected by flow cytometry. Using Western blot and RT-PCR, 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, NAC 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.
Hsin
I-Lun
IL
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Sheu
Gwo-Tarng
GT
Chen
Hung-Hsuan
HH
Chiu
Ling-Yen
LY
Wang
Horng-Dar
HD
Chan
Hsiu-Wen
HW
Hsu
Chung-Ping
CP
Ko
Jiunn-Liang
JL
D000111:Acetylcysteine / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D017382:Reactive Oxygen Species; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism
D017382:Reactive Oxygen Species; D016329:Sp1 Transcription Factor; C509186:TERT protein, human; D019098:Telomerase; D003474:Curcumin; D000111:Acetylcysteine