Involvement of the mitochondrial pathway in p53-independent apoptosis induced by p28GANK knockdown in Hep3B cells.

Abstract:

:It is well known that TP53 may mediate apoptosis triggered by anticancer drugs. However, accumulating evidence indicates that TP53 may be inactivated by mutations and/or deletions in about 50% of human cancers and, as such, may lead to pronounced resistance to therapeutic agents. Thus, the development of new approaches to improve the efficiency of therapeutic agents in cancer cells harboring mutant TP53 may have a significant impact on cancer treatment. It has been reported that knockdown by RNA interference (RNAi) of p28GANK (an alias of the gene PSMD10), a novel oncogene over-expressed in hepatocellular carcinoma (HCC), can induce apoptosis in HepG2, a TP53-intact HCC cell line. Because of the high frequency TP53 mutations in HCC, it is relevant to know whether p28GANK knockdown-induced apoptosis is also operational in TP53-negative HCC cells. Here, we investigated Adsip28GANK-induced apoptosis in the TP53-negative HCC cell line Hep3B. Our results indicate that p28GANK-knockdown induces the generation of reactive oxygen species (ROS), which in turn activates p38. Since p38 can signal to Bax, its activation may lead to mitochondrial transmembrane potential (Delta psi m) loss, cytochrome c release from mitochondria to cytosol, and caspase-9 activation, eventually triggering the mitochondrial pathway of apoptosis.

journal_name

Cytogenet Genome Res

authors

Wang J,Wang XF,Zhang LG,Xie SY,Li ZL,Li YJ,Li HH,Jiao F

doi

10.1159/000227831

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

87-97

issue

2

eissn

1424-8581

issn

1424-859X

pii

000227831

journal_volume

125

pub_type

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