Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemia cell lines.

Abstract:

:We investigated the effect of aphidicolin, an inhibitor of DNA polymerase alpha and delta, on the induction of apoptosis by arabinosyl nucleosides in a human promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with aphidicolin (2 microM) significantly increased the number of morphologically apoptotic cells induced by 1-beta-D arabinofuranosylcytosine (ara-C) during 4 hr of incubation. This is consistent with the appearance of DNA fragmentation as determined quantitatively by diphenylamine or by agarose gel electrophoresis. The inhibition of cell growth on day 3 after drug exposure was correlated with the degree of apoptosis: Such synergistic interaction between aphidicolin and ara-C has also been observed in other human myeloid leukemia cell lines, U937 and KG-1. In addition, the induction of apoptosis by 9-beta-D arabinofuranosyladenine or 9-beta-D arabinofuranosylguanine is augmented by aphidicolin.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Kuwakado K,Kubota M,Hirota H,Adachi S,Matsubara K,Kasai Y,Akiyama Y,Mikawa H

doi

10.1016/0006-2952(93)90631-6

subject

Has Abstract

pub_date

1993-12-03 00:00:00

pages

1909-16

issue

11

eissn

0006-2952

issn

1873-2968

pii

0006-2952(93)90631-6

journal_volume

46

pub_type

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