Demethoxycurcumin-induced DNA Damage Decreases DNA Repair-associated Protein Expression Levels in NCI-H460 Human Lung Cancer Cells.

Abstract

Demethoxycurcumin (DMC) is a key component of Chinese medicine (Turmeric) and has been proven effective in killing various cancer cells. Its role in inducing cytotoxic effects in many cancer cells has been reported, but its role regarding DNA damage on lung cancer cells has not been studied in detail. In the present study, we demonstrated DMC-induced DNA damage and condensation in NCI-H460 cells by using the Comet assay and DAPI staining examinations, respectively. Western blotting indicated that DMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DNA damage response), DNA repair proteins breast cancer 1, early onset (BRCA1), O6-methylguanine-DNA methyltransferase (MGMT), mediator of DNA damage checkpoint 1 (MDC1), and p53 (tumor suppressor protein). DMC activated phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Furthermore, we used confocal laser systems microscopy to examine the protein translocation. The results showed that DMC promotes the translocation of p-p53 and p-H2A.X from the cytosol to the nuclei in NCI-H460 cells. Taken together, DMC induced DNA damage and affected DNA repair proteins in NCI-H460 cells in vitro.

• Authors: Yang-Ching Ko, Jin-Cherng Lien, Hsin-Chung Liu, Shu-Chun Hsu, Hui-Yi Lin, Fu-Shin Chueh, Bin-Chuan Ji, Mei-Due Yang, Wu-Huei Hsu, Jing-Gung Chung
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 5 Pg. 2691-8 (May 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 25964547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Diarylheptanoids
• Neoplasm Proteins
• Curcumin
• demethoxycurcumin

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Curcumin (administration & dosage, analogs & derivatives)
• DNA Damage (drug effects)
• DNA Repair (drug effects)
• Diarylheptanoids
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Neoplasm Proteins (biosynthesis)