A NEW DERIVATIVE OF CAMPTOTHECIN, IRINOTECAN HYDROCHLORIDE (CPT-11) INDUCES PROGRAMMED CELL-DEATH IN LEUKEMIA-LYMPHOMA CELL-LINES

  • Authors:
    • RW HUANG
    • K TAKATSUKI
    • H TSUDA
  • View Affiliations

  • Published online on: October 1, 1993     https://doi.org/10.3892/ijo.3.4.679
  • Pages: 679-685
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Abstract

Irinotecan Hydrochloride (CPT-11) and 7-ethyl-10-hydroxycamptothecin (SN-38), which are both topoisomerase I inhibitors with potent antitumor effects in vivo and in vitro, were tested for the induction of programmed cell death (PCD) in leukemia/lymphoma cell lines. When the human T-cell leukemia cell line HUT-102 and the human promyelocytic leukemia cell line HL-60 cells were exposed to CPT-11, PCD characterized by a DNA fragmentation ladder of 180-200 bp in agarose gel electrophoresis and loss of cell viability was induced. The PCD inducing activity of SN-38, an active metabolite of CPT-11, was much more powerful than that of CPT-11. Besides inducing PCD in HUT-102 and HL-60 cells, SN-38 also induced PCD in the human erythroblast leukemia cell line K-562, which was resistant to CPT-11. Induction of PCD by SN-38 and CPT-11 was dose- and time-dependent. PCD in HUT-102 cells induced by SN-38 was prevented neither by aurintricarboxylic acid (ATA), an endonuclease inhibitor, as determine by DNA electrophoretic profiles and the number of viable cells, nor by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA). The present data suggest that the topoisomerase I inhibitors, SN-38 and CPT-11 exert antitumor activity through induction of PCD in involved cells, at least in part. The PCD-inducing activity of the topoisomerase II inhibitor VP-16 was also tested in the above three cell lines and compared with CPT-11 and SN-38.

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October 1993
Volume 3 Issue 4

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

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Spandidos Publications style
HUANG R, TAKATSUKI K and TSUDA H: A NEW DERIVATIVE OF CAMPTOTHECIN, IRINOTECAN HYDROCHLORIDE (CPT-11) INDUCES PROGRAMMED CELL-DEATH IN LEUKEMIA-LYMPHOMA CELL-LINES. Int J Oncol 3: 679-685, 1993
APA
HUANG, R., TAKATSUKI, K., & TSUDA, H. (1993). A NEW DERIVATIVE OF CAMPTOTHECIN, IRINOTECAN HYDROCHLORIDE (CPT-11) INDUCES PROGRAMMED CELL-DEATH IN LEUKEMIA-LYMPHOMA CELL-LINES. International Journal of Oncology, 3, 679-685. https://doi.org/10.3892/ijo.3.4.679
MLA
HUANG, R., TAKATSUKI, K., TSUDA, H."A NEW DERIVATIVE OF CAMPTOTHECIN, IRINOTECAN HYDROCHLORIDE (CPT-11) INDUCES PROGRAMMED CELL-DEATH IN LEUKEMIA-LYMPHOMA CELL-LINES". International Journal of Oncology 3.4 (1993): 679-685.
Chicago
HUANG, R., TAKATSUKI, K., TSUDA, H."A NEW DERIVATIVE OF CAMPTOTHECIN, IRINOTECAN HYDROCHLORIDE (CPT-11) INDUCES PROGRAMMED CELL-DEATH IN LEUKEMIA-LYMPHOMA CELL-LINES". International Journal of Oncology 3, no. 4 (1993): 679-685. https://doi.org/10.3892/ijo.3.4.679