Bisdemethoxycurcumin induces DNA damage and inhibits DNA repair associated protein expressions in NCI-H460 human lung cancer cells

• Published in: Environmental toxicology Vol. 31; no. 12; pp. 1859 - 1868
• Main Authors: Yu, Chien-Chih, Yang, Su-Tso, Huang, Wen-Wen, Peng, Shu-Fen, Huang, An-Cheng, Tang, Nou-Ying, Liu, Hsin-Chung, Yang, Mei-Due, Lai, Kuang-Chi, Chung, Jing-Gung
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2016; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Agents - pharmacology; bisdemethoxycurcumin; Cell Line, Tumor; Cell Survival - drug effects; comet assay; Curcuma longa; Curcumin - analogs & derivatives; Curcumin - pharmacology; DAPI staining; Deoxyribonucleic acid; Diarylheptanoids; DNA; DNA damage; DNA Damage - drug effects; DNA repair; DNA Repair - drug effects; Histones - metabolism; human lung cancer NCI-H460 cells; Humans; Lung cancer; Lung Neoplasms; Phosphorylation; Protein Transport - drug effects; Proteins; Tumor Suppressor Protein p53 - metabolism; human lung cancer NCI-H460 cells; comet assay; DAPI staining; bisdemethoxycurcumin; DNA damage
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.22187

Nonsmall cell lung carcinoma (NSCLC) is a devastating primary lung tumor resistant to conventional therapies. Bisdemethoxycurcumin (BDMC) is one of curcumin derivate from Turmeric and has been shown to induce NSCLC cell death. Although there is one report to show BDMC induced DNA double strand breaks, however, no available information to show BDMC induced DNA damage action with inhibited DNA repair protein in lung cancer cells in detail. In this study, we tested BDMC‐induced DNA damage and condensation in NCI‐H460 cells by using Comet assay and DAPI staining examinations, respectively and we found BDMC induced DNA damage and condension. Western blotting was used to examine the effects of BDMC on protein expression associated with DNA damage and repair and results indicated that BDMC suppressed the protein levels associated with DNA damage and repair, such as 14‐3‐3σ (an important checkpoint keeper of DDR), O6‐methylguanine‐DNA methyltransferase, DNA repair proteins breast cancer 1, early onset, mediator of DNA damage checkpoint 1 but activate phosphorylated p53 and p‐H2A.X (phospho Ser140) in NCI‐H460 cells. Confocal laser systems microscopy was used for examining the protein translocation and results show that BDMC increased the translocation of p‐p53 and p‐H2A.X (phospho Ser140) from cytosol to nuclei in NCI‐H460 cells. In conclusion, BDMC induced DNA damage and condension and affect DNA repair proteins in NCI‐H460 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1859–1868, 2016.