The benzoylurea derivative F13 inhibits cell growth, migration and invasion through inducing expression of ERK1/2-mediated RECK in fibrosarcoma HT-1080 cells.
3-Bromoacetamino-4-methoxy-benzoylurea (F13) is a benzoylurea derivative selected from the library of small molecule tubulin ligands. Our earlier data showed that F13 had lost the capacity to interrupt microtubule dynamics while reserving anticancer activity. In this study, we found that F13 greatly inhibited cell proliferation in various human cancer cells. At concentrations of more than 1 microg/ml, F13 markedly slowed growth and induced apoptosis in HT-1080 cells. This apoptosis occurred through cleavages of caspase 3 and PARP. At low concentrations (< or =1 microg/ml), F13 reduced the migration, adhesion, and invasion of HT-1080 cells. In addition, F13 downregulated the activities of matrix metalloproteinase-2/9 (MMP-2/9) in a culture supernatant. This was found to occur through the upregulation of the reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a membrane-anchored inhibitor of MMPs, which acts by reducing ERK1/2 phosphorylation. Our data suggested that F13 might act as a novel RECK inducer, inhibiting cancerous processes with the inactivation of MMP-2/9 by the induction of RECK through the inhibition of ERK1/2 signalling transduction.
Jin
Haixia
H
Departments of Oncology and Pharmacology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Ren
Kaihuan
K
He
Hong-Wei
HW
Liu
Xia
X
Song
Dan-Qing
DQ
Shao
Rong-Guang
RG
D000083:Acetanilides / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D058851:GPI-Linked Proteins; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020935:MAP Kinase Signaling System; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C549814:3-bromoacetamino-4-methoxybenzoylurea; D000083:Acetanilides; D000970:Antineoplastic Agents; D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D014508:Urea; D011065:Poly(ADP-ribose) Polymerases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D020782:Matrix Metalloproteinases