Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-kappaB pathway.

Abstract:

:We recently found that simvastatin can modulate the nuclear factor-kappaB (NF-kappaB) activation pathway, but whether other statins have similar effects to those of simvastatin is unknown. Therefore, we evaluated the effect six different statins on TNF-induced NF-kappaB activation in human myeloid leukemia cells. We then determined whether the combination of statins and standard chemotherapeutic agents could overcome chemoresistance and augment apoptosis. Of the six statins evaluated, only the natural statins (simvastatin, mevastatin, lovastatin, and pravastatin), not the synthetic statins (fluvastatin and atorvastatin), inhibited TNF-induced NF-kappaB activation. Simvastatin suppressed the NF-kappaB activation and potentiated the apoptosis induced by doxorubicin, paclitaxel, and 5-fluorouracil. These results suggest that different statins behave differently from one another and that they may be useful in overcoming chemoresistance.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Ahn KS,Sethi G,Aggarwal BB

doi

10.1016/j.bcp.2007.10.010

subject

Has Abstract

pub_date

2008-02-15 00:00:00

pages

907-13

issue

4

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(07)00689-2

journal_volume

75

pub_type

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