Introduction: Trabectedin (Yondelis, ET-743) is a semi-synthetic natural product derived from the marine tunicate Ecteinascidia turbinate. The mechanism of ...
Annals of Oncology 24 (Supplement 1): i30–i32, 2013 doi:10.1093/annonc/mdt047.3
Poster session 5. Translational research P05:03
P53 MODULATES TRABECTEDIN MEDIATED CYTOTOXICITY IN GLIOBLASTOMA MULTIFORME CELLS (U-87MG AND T98G)
abstracts
Introduction: Trabectedin (Yondelis, ET-743) is a semi-synthetic natural product derived from the marine tunicate Ecteinascidia turbinate. The mechanism of action of Trabectedin has yet to be fully defined but DNA appears to be the primary target. DNA damage can lead to the activation of p53 which is one of the important components of DNA damage sensing systems. Forty percent of glioblastoma multiforme (GBM) tumors have p53 mutations. These mutations are also strongly associated with malignant progression of GBM. However, the role of p53 in determining the sensitivity of tumors to chemotherapeutic agents is still not very
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E. Bozkurt1, H. Atmaca1, S. Uzunoglu1, R. Uslu2, B. Karaca2 1 Celal Bayar University, Manisa, Turkey, 2Ege University, Izmir, Turkey
clear. The objective of this study is to investigate whether the viability of trabectedin treated U-87MG (wt-p53) and T98G (mut-p53) cell cultures are differentiated by p53 status. Methods: Real time monitoring of cell proliferation was assessed after the exposure of the increasing concentrations of trabectedin (0.1-100 nM for 72 hours) in U87MG and T98G cells by xCELLigence system. Pifithrin-α, an inhibitor of the p53, was applied at a concentration of 30 µM. p53 protein expressions were determined by Western blot. Results: Trabectedin inhibited cell proliferation in a dose and time dependent manner in both cell lines. The IC50 values for a 48 h treatment of Trabectedin in U87MG and T98G cells were 5 and 13 nM, respectively. In trabectedin treated U-87MG cells, there was a significant increase in p53 protein expression, while there was no change in trabectedin treated T98G cells. Trabectedin mediated cytotoxicity was inhibited in the presence of pifithrin-α in U87-MG cells having wild type p53, however in pifithrin-α treated T98G cells there was no change in trabectedin mediated cytotoxicity. These data imply that cytotoxic effect of trabectedin was dependent p53. Conclusions: p53 may be a selective marker for trabectedin treatment in GBM. More detailed studies are needed to assess the validity of p53 as a marker for trabectedin sensitivity in GBM.
