PTD4-apoptin protein therapy inhibits tumor growth in vivo.
Apoptin protein harbors tumor-selective cell death activity, which makes it a potential anticancer therapy candidate. This study reports an apoptin therapy approach based on protein transduction domain 4 (PTD4)-mediated transduction of recombinant apoptin protein. In vitro, the PTD4-apoptin fusion protein is located in the nucleus and induces cell death in, e.g., human hepatocarcinoma HepG2 cells. In normal human L-02 hepatocytes, PTD4-apoptin protein retained mainly cytoplasmic and did not induce detectable levels of cell death, illustrating that the PTD4 domain does not affect apoptin's tumor-selective characteristics. In vivo, liver, cervix and gastric carcinoma xenografts treated with PTD4-apoptin protein for 6 days via the tumor epidermis exhibited a significant tumor growth inhibition because of apoptin-mediated cell death. In addition, treatment of human hepatocarcinoma xenografts during 3 weeks showed that PTD4-apoptin protein has significant anticancer activity, whereas control treatment with PTD4-enhanced green fluorescence protein or saline did not. Cell death and disruption of the tumor integrity were apparent in the PTD4-apoptin transduced xenografted tumors. As important, although PTD4-apoptin protein could be detected in the epidermal tissue covering the subcutaneous tumor tissue and in several organs, such as liver and brain, of the treated mice, no tissue disruption or signs of cell death could be detected. Our in vivo data reveal that apoptin protein delivery constitutes a novel powerful and safe anticancer therapy.
Sun
Jun
J
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Yan
Ying
Y
Wang
Xiao-Ting
XT
Liu
Xiao-Wen
XW
Peng
Dong-Jun
DJ
Wang
Min
M
Tian
Jun
J
Zong
Yi-Qiang
YQ
Zhang
Ying-Hui
YH
Noteborn
Mathieu H M
MH
Qu
Shen
S