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Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt.

Abstract：

:Bee venom (BV) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in BV-induced apoptosis are still uncharacterized in human leukemic cells. In the present study, we report that BV induces apoptosis in leukemic U937 cells through downregulation of ERK and Akt signal pathway. Furthermore, BV-induced apoptosis was accompanied by downregulation of Bcl-2, activation of caspase-3 and a subsequent poly(ADP-ribose)polymerase (PARP) cleavages. The induction of apoptosis also was accompanied by the downregulation of the inhibitor of apoptosis protein (IAP) family proteins. Caspase-3 inhibitor, z-DEVD-fmk, was significantly capable of restoring cell viability and BV-induced apoptosis through caspase-3 activation was significantly attenuated in Bcl-2-overexpressing cells. These results indicate that downregulation of Bcl-2 plays a major role in the initiation as an activator of a caspase-3 involved with BV-induced apoptosis. BV also triggered the activation of p38 MAPK and JNK, and downregulation of ERK and Akt. PD98059 (an inhibitor of ERK) or LY294002 (an inhibitor of Akt), but not an inhibitor of p38 MAPK and JNK, significantly decreased cell viability and increased lactate dehydrogenase (LDH) release. The results indicated that key regulators in BV-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of the ERK and Akt signal pathway.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Moon DO,Park SY,Heo MS,Kim KC,Park C,Ko WS,Choi YH,Kim GY

doi

10.1016/j.intimp.2006.07.027

subject

Has Abstract

pub_date

2006-12-05 00:00:00

pages

1796-807

issue

12

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(06)00230-X

journal_volume

6

pub_type

杂志文章

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