Stimulation of interleukin-1beta-converting enzyme activity during growth inhibition by CPT-11 in the human myeloid leukemia cell line K562.
Camptothecin (CPT) was first extracted from Camptotheca acuminata and has a strong antitumor effect. Its water-soluble derivative, CPT-11, has higher therapeutic efficacy and less toxicity than CPT. Recently, CPT-treated cells have been shown to undergo apoptosis. However, the mechanism of induction of apoptosis by CPT has not been characterized in detail in any type of cells. On the other hand, interleukin-1beta-converting enzyme (ICE) is a mammalian homologue of CED3, a protein required for apoptosis in the nematode Caenorhabditis elegans. To determine how CPT-11 brings about cell death by apoptosis, we investigated the effects of CPT-11 on the expression of ICE activity in K562 cells, which represent human myeloid leukemia cells. The proliferation of K562 cells was shown to be inhibited by the presence of CPT-11 in the culture medium. We also found that the levels of mRNA for ICE in the cells were increased in the presence of CPT-11. Furthermore, we demonstrated that when CPT-11 was added to the culture medium, apoptosis of K562 cells was clearly detected in situ. These features suggested that CPT-11 enhances the apoptotic cell death in K562 cells and that a part of induction of apoptosis by CPT-11 may be correlated with the stimulation of the ICE activity.
Shibata
Y
Y
Department of Biochemistry, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba, 271.
Takiguchi
H
H
Tamura
K
K
Yamanaka
K
K
Tezuka
M
M
Abiko
Y
Y
D017209:Apoptosis; D001483:Base Sequence; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017403:In Situ Hybridization; D000077146:Irinotecan; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D000077146:Irinotecan; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D002166:Camptothecin