mda-7/IL-24 induces apoptosis in human HepG2 hepatoma cells by endoplasmic reticulum stress.
mda-7/IL-24 shows tumor-suppressor activity in a broad spectrum of human cancer cells. However, the molecular mechanism by which mda-7/IL-24 induces apoptosis is not well understood and most likely involves different pathways depending on the tumor. We examined the apoptotic effect of the adenovirus-mediated mda-7/IL-24 (Ad.mda-7) on human HepG2 hepatoma cells. We found that blocking the endoplasmic reticulum (ER) stress inhibited apoptosis induced by Ad.mda-7 and down-regulated the expression of caspase-12, Bax and caspase-3. The treatment of subcutaneous tumor xenografts of HepG2 cells with Ad.mda-7 inhibited tumor growth and angiogenesis. As in the in vitro studies, we found that blocking ER stress prevented Ad.mda-7 from inducing apoptosis in liver cancer cells in vivo. Our studies suggest that Ad.mda-7 induces apoptosis of HepG2 cells mainly through activation of the ER stress pathway.
Zhang
Xiaofeng
X
Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, People's Republic of China.
Kang
Xiaoyan
X
Shi
Lehua
L
Li
Jin
J
Xu
Wen
W
Qian
Haihua
H
Wu
Mengchao
M
Yin
Zhengfeng
Z
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010957:Plasmids; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099180:Interleukin-24
D053454:Caspase 12; D053148:Caspase 3; D007378:Interleukins; D051028:bcl-2-Associated X Protein; D000099180:Interleukin-24; C494826:BAX protein, human; C506444:CASP12 protein, human