Mitosis-arresting effect of the calcium channel inhibitor SK&F 96365 on human leukemia cells.

Abstract:

:The effect of SK&F 96365 (1-(beta-[3-(4-methoxyphenyl)propoxyl]-4- methoxyphenethyl)-1H-imidazole hydrochloride), a recently synthesized inhibitor of receptor-mediated calcium entry, was investigated on human hematopoietic cell lines. We found that treatment of the T-cell leukemia line Jurkat with SK&F 96365 inhibited the Ca2+ influx triggered by antibodies against the CD3/TCR complex, while the inositol trisphosphate-dependent Ca2+ release from intracellular stores remained intact. A 50% inhibition of the Ca2+ influx was obtained with 5 microM SK&F 96365, while higher concentrations of the drug blocked the CD3-dependent Ca2+ influx completely. In addition to its blocking of the Ca2+ influx, treatment with SK&F 96365 was found to accumulate mitotic cells. The drug (5 microM) imposed a total cell cycle arrest in G2/M. The mitosis block could be reversed by removal of the inhibitor from the cultures, while elevation of intracellular or extracellular Ca2+ did not restore cell cycle progression. This suggests that the cell cycle block induced by SK&F 96365 is not directly related to its action as an inhibitor of receptor-mediated calcium entry. Our findings indicate that SK&F 96365, in addition to its ability to inhibit receptor-triggered Ca2+ influx, offers a new method for imposing a reversible mitosis arrest in hematopoietic cell lines.

journal_name

Exp Cell Res

authors

Nordström T,Nevanlinna HA,Andersson LC

doi

10.1016/0014-4827(92)90103-f

keywords:

subject

Has Abstract

pub_date

1992-10-01 00:00:00

pages

487-94

issue

2

eissn

0014-4827

issn

1090-2422

pii

0014-4827(92)90103-F

journal_volume

202

pub_type

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