Bisdemethoxycurcumin induces DNA damage and inhibits DNA repair associated protein expressions in NCI-H460 human lung cancer cells.
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.
School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
Chien-Chih
CC
Yu
Department of Radiology, China Medical University Hospital, Taichung, 404, Taiwan.|School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
Su-Tso
ST
Yang
Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
Wen-Wen
WW
Huang
Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
Shu-Fen
SF
Peng
Department of Nursing, St. Mary's Junior college of Medicine, Nursing and Management, Yilan, 266, Taiwan.
An-Cheng
AC
Huang
Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
Nou-Ying
NY
Tang
Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
Hsin-Chung
HC
Liu
Department of Surgery, China Medical University Hospital, Taichung, Taiwan.
Mei-Due
MD
Yang
School of Medicine, China Medical University Hospital, Taichung, 404, Taiwan.|Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, Tainan, 717, Taiwan.
Kuang-Chi
KC
Lai
Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Wu Feng, Taichung, 404, Taiwan.
Jing-Gung
JG
Chung
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D036381:Diarylheptanoids; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D036381:Diarylheptanoids; C468783:H2AX protein, human; D006657:Histones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C034786:bisdemethoxycurcumin; D003474:Curcumin
DAPI staining; DNA damage; bisdemethoxycurcumin; comet assay; human lung cancer NCI-H460 cells