title: Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells.
abstract: OBJECTIVE
  Curcumin is a lead compound of the rhizomes ofCurcuma longaand possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability.
  
  
  METHODS
  A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels.
  
  
  RESULTS
  DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9.
  
  
  CONCLUSIONS
  DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein.
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT 21144, Jalan Sungai Long, Bandar Sungai Long, Cheras, 43000 Kajang, Selangor Malaysia.
authors.forename: Norlaily Mohd
authors.initials: NM
authors.lastname: Ali
authors.affiliation: China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Jalan Sunsuria, Bandar Sunsuria, 43900 Sepang, Selangor Malaysia.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: UKM Molecular Biology Institute (UMBI), UKM Medical Centre, Jalan Yaa'cob Latiff, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia.
authors.forename: Nadiah
authors.initials: N
authors.lastname: Abu
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT 21144, Jalan Sungai Long, Bandar Sungai Long, Cheras, 43000 Kajang, Selangor Malaysia.
authors.forename: Kian Lam
authors.initials: KL
authors.lastname: Lim
authors.affiliation: Department of Agriculture Genetics and Breeding, College of Agriculture and Applied Biology, Cantho University, 3/2 Street, CanTho City, Vietnam.
authors.forename: Huynh
authors.initials: H
authors.lastname: Ky
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 Serdang, Selangor Malaysia.
authors.forename: Ahmad Zaim Mat
authors.initials: AZM
authors.lastname: Pauzi
authors.affiliation: School of Biomedical Sciences, The University of Nottingham Malaysia Campus, JalanBroga, 43500 Semenyih, Selangor Malaysia.
authors.forename: Wan Yong
authors.initials: WY
authors.lastname: Ho
authors.affiliation: Institute of Bioscience, University Putra Malaysia, 43400 Serdang, Selangor Malaysia.
authors.forename: Sheau Wei
authors.initials: SW
authors.lastname: Tan
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT 21144, Jalan Sungai Long, Bandar Sungai Long, Cheras, 43000 Kajang, Selangor Malaysia.
authors.forename: Han Kiat
authors.initials: HK
authors.lastname: Alan-Ong
authors.affiliation: Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, 26300 Kuantan Pahang, Malaysia.
authors.forename: Seema
authors.initials: S
authors.lastname: Zareen
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 Serdang, Selangor Malaysia.
authors.forename: Noorjahan Banu
authors.initials: NB
authors.lastname: Alitheen
authors.affiliation: Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, 26300 Kuantan Pahang, Malaysia.
authors.forename: M Nadeem
authors.initials: MN
authors.lastname: Akhtar
keywords: Apoptosis; CDC2 phosphorylation; Cell cycle arrest; DK1; ROS