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Induction of differentiation and enhancement of vincristine sensitivity of human erythroleukemia HEL cells by vesnarinone, a positive inotropic agent.

Abstract：

:We examined the effect of vesnarinone, an oral cardiotonic, on the growth and differentiation of human myeloid leukemia cells. Vesnarinone alone markedly induced erythroid differentiation of HEL cells. All-trans-retinoic acid also induced erythroid differentiation of the cells, and the differentiation was greatly enhanced by combined treatment with vesnarinone and retinoic acid. HEL cells are highly resistant to some anticancer drugs, including vincristine, but treatment with vesnarinone greatly increased the sensitivity of HEL cells to vincristine. Enhancement of vincristine sensitivity by vesnarinone was not as significant for other leukemia cells. Expression of P-glycoprotein in HEL cells was effectively inhibited by vesnarinone, suggesting that the restoration of vincristine sensitivity is associated with decrease of P-glycoprotein expression in HEL cells. The plasma level of vesnarinone required to induce differentiation of leukemia cells is 30 micrograms/mL, which could be achieved with oral administration. These results suggest that vesnarinone should be useful in differentiation therapy for some types of myelogenous leukemia.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Sato S,Tomoyasu S,Okabe-Kado J,Hozumi M,Tsuruoka N,Nakai S,Adachi M,Honma Y

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

37-42

issue

1

eissn

0301-472X

issn

1873-2399

journal_volume

24

pub_type

杂志文章

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