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Chidamide-induced ROS accumulation and miR-129-3p-dependent cell cycle arrest in non-small lung cancer cells
- Source :
- Phytomedicine : international journal of phytotherapy and phytopharmacology. 56
- Publication Year :
- 2018
-
Abstract
- Background Epigenetic therapy is a promising popular treatment modality for various cancers. Histone modification and miRNA should not be underestimated in lung cancer. This study aimed to investigate whether chidamide, a histone deacetylase inhibitor (HDACi), which inhibits telomerase activity and induces cell cycle arrest, influences ROS and miRNA production in non-small cell lung cancer (NSCLC) cells. Methods H1355 and A549 were treated with chidamide. The analysis of DNA content was measured by FACSCalibur equipped with a 488 nm laser. H1355 cells were transfected with miR-129-3p mimic by Lipofectamine2000. Telomerase activity was performed on the telomeric repeat amplification protocol (TRAP) assay. Detection of thymidylate synthase (TS), p21, p53, pRB, and β-actin, were performed by western blot analysis. Results Our data showed that expression of TS, p21, and pRB were altered in the presence of chidamide by PCR and western blot. Using BrdU-incorporation analysis, we found that chidamide induced G1 arrest through the regulation of the TS gene by miR-129-3p. Chidamide was shown to suppress telomerase activity in the TRAP assay and reduced the expression of human telomerase reverse transcriptase (hTERT) by PCR and q-PCR in H1355 and A549 cells. Chidamide increased the generation of reactive oxygen species (ROS) by flow cytometry. N-acetyl cysteine (NAC), a ROS scavenger, attenuated chidamide-induced telomerase activity inhibition. Conclusion Chidamide repressed telomerase activity through ROS accumulation and cell cycle arrest by miR-129-3p upregulation in both H1355 and A549 cells. This is the first study to demonstrate that chidamide induces miR-129-3p upregulation and ROS accumulation, leading to cell cycle arrest.
- Subjects :
- Telomerase
Cell cycle checkpoint
Lung Neoplasms
medicine.drug_class
Pharmaceutical Science
Aminopyridines
Antineoplastic Agents
Flow cytometry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Chidamide
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Drug Discovery
medicine
Humans
Telomerase reverse transcriptase
030304 developmental biology
Pharmacology
A549 cell
0303 health sciences
medicine.diagnostic_test
Chemistry
Histone deacetylase inhibitor
Transfection
Cell Cycle Checkpoints
Gene Expression Regulation, Neoplastic
Histone Deacetylase Inhibitors
MicroRNAs
Complementary and alternative medicine
A549 Cells
030220 oncology & carcinogenesis
Benzamides
Cancer research
Molecular Medicine
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 1618095X
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Accession number :
- edsair.doi.dedup.....d2f70b59221169b031f658638b7848af