Oct 31, 2009

Effects of cisplatin on matrix metalloproteinase-2 in transformed thyroid cells

Biochemical Pharmacology
L UrsoS Marsigliante

Abstract

We investigated the effects of cisplatin (cisPt) on matrix metalloproteinase-2 (MMP-2) gelatinolitic activity in transformed PC E1Araf rat thyroid cells. Cells incubated with increasing cisPt concentrations showed dose- and time-dependent decrease of the MMP-2 protein and activity. CisPt provoked the translocation from the cytosol to the plasma membrane of atypical protein kinase C-zeta (PKC-zeta) and the activation of PKB/AKT. The effect of cisPt on MMP-2 was dependent on PKC-zeta activation since it was potentiated by a myristoylated PKC-zeta pseudo substrate peptide or by PKC-zeta down-regulation by siRNA. Moreover, MMP-2 activity modulation by cisPt was also dependent on PKB/AKT activation since it was decreased by PKB/AKT down-regulation by siRNA or by pharmacological inhibition of PI3K, thus indicating the importance of the balance of PKB/AKT and PKC-zeta in regulating the cisPt effect on MMP-2 activity. The PC E1Araf cells displayed a migratory capacity that was blocked by MMP-2 down-regulation using siRNA or pharmacological inhibition. The inhibition of cell migration was also obtained with cisPt; in cisPt-treated cells the administration of MMP-2 active protein was able to restore cell migration capacity. In conclusion...Continue Reading

  • References29
  • Citations4

References

  • References29
  • Citations4

Mentioned in this Paper

Antineoplastic Agents
Apoptosis, Intrinsic Pathway
RNA, Small Interfering
Cell Migration Inhibition Function
AP5Z1 gene
Pseudo brand of pseudoephedrine
Matrix Metalloproteinase 2
MMP-2 Activity
Process of Secretion
Gene Expression Regulation, Enzymologic

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