Involvement of the mitochondrial pathway in p53-independent apoptosis induced by p28GANK knockdown in Hep3B cells.
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.
Wang
J
J
Department of Biotechnology, Binzhou Medical College, Binzhou, PR China.
Wang
X F
XF
Zhang
L G
LG
Xie
S Y
SY
Li
Z L
ZL
Li
Y J
YJ
Li
H H
HH
Jiao
F
F
D017209:Apoptosis; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases; D053453:Caspase 9; D046988:Proteasome Endopeptidase Complex