Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Inhibition of Apoptosis is Responsible for the Acquired Resistance of K562 Cells to Cisplatin

  • Lee, Soo-Yong (Biotransformation and Bioanalysis Research Center, Korea Institute of Science and Technology) ;
  • Kim, Dong-Hyun (Biotransformation and Bioanalysis Research Center, Korea Institute of Science and Technology)
  • Published : 2004.06.01
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Abstract

In all attempt to elucidate the role of apoptosis in drug resistance, cisplatin-resistant human chronic myelogenous leukemia (CML) K562 cells (K562/CDDP) were established and compared with drug sensitive parent cells (K562) in the induction of apoptosis. K562/CDDP cells were 5-fold more resistant to cisplatin compared to K562 cells. In addition, K562/CDDP cells were significantly more resistant to apoptois as judged by DNA fragmentation and DAPI staining. K562/CDDP cells exhibited decreased proleolytic activity of caspase-3 and this was further demonstrated by decreased cleavage of its substrate poly (ADP-ribose) polymerase (PARR- Western blot analysis showed that K562/CDDP cells had longer sustained levels of BCL-$X_L$ whereas no difference was noted in the level of Bcl-2. the translocation of Bax to mitochondria was significantly delayed in K562/CDDP cells. These results suggest that the reduced translocation of Bax and the sustained expression of BCL-$X_L$ may cause resistance to apoptosis through prevention of mitochondria release of cytochrome c, which subsequently induces reduction of caspase-3 activity and that this response is partly responsible for the acquired resistance to cisplatin ill K562 cells.

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References

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