BCL-2 GENE PREVENTS INDUCTION OF APOPTOSIS IN L1210 MURINE LEUKEMIA-CELLS BY SN-38, A METABOLITE OF THE CAMPTOTHECIN DERIVATIVE CPT-11

  • Authors:
    • S KONDO
    • D YIN
    • T MORIMURA
    • J TAKEUCHI
  • View Affiliations

  • Published online on: March 1, 1994     https://doi.org/10.3892/ijo.4.3.649
  • Pages: 649-654
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Abstract

New camptothecin (CPT) derivatives have recently been synthesized following the finding that CPT has strong antitumor activity due to its inhibition of topoisomerase I through the formation of stable topoisomerase I-DNA cleavable complexes, but has not been clinically used due to its pronounced toxicity. 7-ethyl-10-hydroxy-CPT (SN-38), a metabolite of the CPT derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-CPT(CPT-11), plays an essential role in mediating the antitumor effect of CPT-11. However, the reasons for the cytotoxicity of SN-38 remain unclear. In this study, we demonstrated using results of DNA fragmentation assay and cell cycle analysis that SN-38 and CPT both induce apoptosis in L1210 murine leukemia cells. We demonstrated in addition that enforced expression of the bcl-2 gene in L1210 cells by MPZenNeo (bcl-2) retroviral gene transfer increased resistance to the apoptosis induced by SN-38 and CPT. These findings suggest the possibility that the bcl-2 gene impedes the activity of a common pathway for apoptosis induced by SN-38 and CPT.

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March 1994
Volume 4 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
KONDO S, YIN D, MORIMURA T and TAKEUCHI J: BCL-2 GENE PREVENTS INDUCTION OF APOPTOSIS IN L1210 MURINE LEUKEMIA-CELLS BY SN-38, A METABOLITE OF THE CAMPTOTHECIN DERIVATIVE CPT-11. Int J Oncol 4: 649-654, 1994
APA
KONDO, S., YIN, D., MORIMURA, T., & TAKEUCHI, J. (1994). BCL-2 GENE PREVENTS INDUCTION OF APOPTOSIS IN L1210 MURINE LEUKEMIA-CELLS BY SN-38, A METABOLITE OF THE CAMPTOTHECIN DERIVATIVE CPT-11. International Journal of Oncology, 4, 649-654. https://doi.org/10.3892/ijo.4.3.649
MLA
KONDO, S., YIN, D., MORIMURA, T., TAKEUCHI, J."BCL-2 GENE PREVENTS INDUCTION OF APOPTOSIS IN L1210 MURINE LEUKEMIA-CELLS BY SN-38, A METABOLITE OF THE CAMPTOTHECIN DERIVATIVE CPT-11". International Journal of Oncology 4.3 (1994): 649-654.
Chicago
KONDO, S., YIN, D., MORIMURA, T., TAKEUCHI, J."BCL-2 GENE PREVENTS INDUCTION OF APOPTOSIS IN L1210 MURINE LEUKEMIA-CELLS BY SN-38, A METABOLITE OF THE CAMPTOTHECIN DERIVATIVE CPT-11". International Journal of Oncology 4, no. 3 (1994): 649-654. https://doi.org/10.3892/ijo.4.3.649