title: N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells.
abstract: 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.
authors.affiliation: Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: I-Lun
authors.initials: IL
authors.lastname: Hsin
authors.forename: Gwo-Tarng
authors.initials: GT
authors.lastname: Sheu
authors.forename: Hung-Hsuan
authors.initials: HH
authors.lastname: Chen
authors.forename: Ling-Yen
authors.initials: LY
authors.lastname: Chiu
authors.forename: Horng-Dar
authors.initials: HD
authors.lastname: Wang
authors.forename: Hsiu-Wen
authors.initials: HW
authors.lastname: Chan
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Hsu
authors.forename: Jiunn-Liang
authors.initials: JL
authors.lastname: Ko
mesh_terms: 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
chemical_list: D017382:Reactive Oxygen Species; D016329:Sp1 Transcription Factor; C509186:TERT protein, human; D019098:Telomerase; D003474:Curcumin; D000111:Acetylcysteine