title: Curcumin induces apoptosis and suppresses invasion through MAPK and MMP signaling in human monocytic leukemia SHI-1 cells.
abstract: BACKGROUND
  Curcumin is a polyphenolic compound extracted from rhizomes of the tropical plant Curcuma longa L. (Zingiberaceae) and it has antitumor, antioxidative, and anti-inflammatory effects. However, its effects on leukemia cell proliferation and invasion are not clear.
  
  
  OBJECTIVE
  This study investigates the effects of curcumin on acute monocytic leukemia SHI-1 cells at the molecular level.
  
  
  METHODS
  The effects of SHI-1 cells treated with 6.25-25 μM curcumin for 12-48 h were measured by MTT assay, flow cytometry, and Matrigel transwell assay; the underlying molecular mechanisms were assessed by quantitative PCR, Western blotting, and gelatin zymography.
  
  
  RESULTS
  Treatment of SHI-1 cells with curcumin inhibited cell proliferation in a dose- and time-dependent manner, and the IC50 values at 12, 24, and 48 h were 32.40, 14.13, and 9.67 μM. Curcumin inhibited SHI-1 cell proliferation by arresting the cells in the S-phase, increasing the number of Annexin V-FITC(+)/PI(-) cells and promoting the loss of △Ψm. The results of PCR and Western blotting showed that curcumin increased the FasL mRNA level; inhibited Bcl-2, NF-κB, and ERK expression; and activated P38 MAPK, JNK, and caspase-3. Additionally, curcumin partially suppressed SHI-1 cell invasion and attenuated the mRNA transcription and secretion of MMP-2 and MMP-9.
  
  
  CONCLUSIONS
  This study demonstrates that curcumin not only induces SHI-1 cell apoptosis, possibly via both intrinsic and extrinsic pathways triggered by JNK, P38 MAPK and ERK signaling, but also partially suppresses SHI-1 cell invasion, likely by reducing the levels of transcription and secretion of MMP-2 and MMP-9.
authors.affiliation: a First Clinical College, Nanjing University of Chinese Medicine , Nanjing , China .
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Zhu
authors.affiliation: b Leukemia Research Unit, Jiangsu Institute of Hematology, 1st Affiliated Hospital of Soochow University , Suzhou , China , and.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Dai
authors.affiliation: a First Clinical College, Nanjing University of Chinese Medicine , Nanjing , China .|c Department of Hematology , 1st Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing , China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Shen
authors.affiliation: a First Clinical College, Nanjing University of Chinese Medicine , Nanjing , China .
authors.forename: Ou
authors.initials: O
authors.lastname: Ji
authors.affiliation: a First Clinical College, Nanjing University of Chinese Medicine , Nanjing , China .
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: a First Clinical College, Nanjing University of Chinese Medicine , Nanjing , China .
authors.forename: Yun-Liang
authors.initials: YL
authors.lastname: Zhai
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D007948:Leukemia, Monocytic, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D003474:Curcumin
keywords: Antitumor; matrix metalloproteinase; mitogen-activated protein kinase