Autor: |
Kubota, Masaru, Usami, Ikuya, Watanabe, Ken-ichiro, Sawada, Machiko, Kataoka, Akihiro, Koishi, Seiji, Lin, Ying-Wei, Akiyama, Yuichi, Furusho, Kenshi |
Zdroj: |
Experimental Cell Research; August 1997, Vol. 235 Issue: 1 p138-144, 7p |
Abstrakt: |
We selected an apoptosis-resistant subline (VC-33) in a human promyelocytic leukemia cell line, HL-60, by alternating exposure to camptothecin (CPT) and etoposide (VP-16). When wild-type (WT) and VC-33 cells were incubated with various concentrations of either CPT or VP-16 for 4 h, VC-33 showed several-fold resistance to apoptosis induced by these agents in comparison with WT cells. VC-33 cells also exhibited cross-resistance to apoptosis induced by 1-β-d-arabinofuranosylcytosine, hydroxyurea, a calcium ionophore (A23187), cycloheximide, or UV irradiation. The levels of protein–DNA cross-linking induced by CPT or VP-16, and the amounts of ara–CTP generation, tended to be smaller in VC-33 cells, but the difference was not sufficient to explain the difference in the sensitivity to apoptosis. The initial rise of intracellular calcium ions with A23187 and the expression of P-glycoprotein, Bcl-2, and Bcl-Xlwere comparable between WT and VC-33 cells. This mutant may represent a new phenotype of resistance to apoptosis induced by a variety of agents, and may thus be useful in the study of the mechanisms of apoptosis. |
Databáze: |
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