title: 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.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Yang-Ching
authors.initials: YC
authors.lastname: Ko
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Hsin-Chung
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, R.O.C.
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C. General Education Center, Chienkuo Technology University, Changhua, Taiwan, R.O.C.
authors.forename: Bin-Chuan
authors.initials: BC
authors.lastname: Ji
authors.affiliation: Department of Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Mei-Due
authors.initials: MD
authors.lastname: Yang
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw hsuwh@mail.cmuh.org.tw.
authors.forename: Wu-Huei
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C. Department of Biotechnology, Asia University, Wu feng, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw hsuwh@mail.cmuh.org.tw.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D036381:Diarylheptanoids; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis
chemical_list: D036381:Diarylheptanoids; D009363:Neoplasm Proteins; D003474:Curcumin; C050229:demethoxycurcumin
keywords: DAPI staining; DNA damage; Demethoxycurcumin (DMC); comet assay; human lung cancer NCI-H460 cells