PMID- 26031207
OWN - NLM
STAT- MEDLINE
DCOM- 20160119
LR  - 20150929
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 231
IP  - 1
DP  - 2016 Jan
TI  - Cell-penetrating and endoplasmic reticulum-locating TAT-IL-24-KDEL fusion protein 
      induces tumor apoptosis.
PG  - 84-93
LID - 10.1002/jcp.25054 [doi]
AB  - Interleukin-24 (IL-24) is a unique IL-10 family cytokine that could selectively 
      induce apoptosis in cancer cells without harming normal cells. Previous research 
      demonstrated that intracellular IL-24 protein induces an endoplasmic reticulum 
      (ER) stress response only in cancer cells, culminating in apoptosis. In this 
      study, we developed a novel recombinant fusion protein to penetrate into cancer 
      cells and locate on ER. It is composed of three distinct functional domains, 
      IL-24, and the targeting domain of transactivator of transcription (TAT) and an 
      ER retention four-peptide sequence KDEL (Lys-Asp-Glu-Leu) that link at its NH2 
      and COOH terminal, respectively. The in vitro results indicated that 
      TAT-IL-24-KDEL inhibited growth in bladder cancer cells, as well as in non-small 
      cell lung cancer cell line and breast cancer cell line, but the normal human lung 
      fibroblast cell line was not affected, indicating the cancer specificity of 
      TAT-IL-24-KDEL. Western blot analysis showed that apoptosis activation was 
      induced by TAT-IL-24-KDEL through the ER stress-mediated cell death pathway. 
      Treatment with TAT-IL-24-KDEL significantly inhibited the growth of human H460 
      xenografts in nude mice, and the tumor growth inhibition was correlated with 
      increased hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) staining. These findings 
      suggest that the artificially designed recombinant fusion protein TAT-IL-24-KDEL 
      may be highly effective in cancer therapy and worthy of further evaluation and 
      development.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Zhang, Jian
AU  - Zhang J
AD  - State Key Laboratory of Bioreactor Engineering, New World Institute of 
      Biotechnology, East China University of Science and Technology, Shanghai, 
      People's Republic of China.
FAU - Sun, Aiyou
AU  - Sun A
AD  - State Key Laboratory of Bioreactor Engineering, New World Institute of 
      Biotechnology, East China University of Science and Technology, Shanghai, 
      People's Republic of China.
FAU - Xu, Rui
AU  - Xu R
AD  - State Key Laboratory of Bioreactor Engineering, New World Institute of 
      Biotechnology, East China University of Science and Technology, Shanghai, 
      People's Republic of China.
FAU - Tao, Xinyi
AU  - Tao X
AD  - State Key Laboratory of Bioreactor Engineering, New World Institute of 
      Biotechnology, East China University of Science and Technology, Shanghai, 
      People's Republic of China.
FAU - Dong, Yuguo
AU  - Dong Y
AD  - State Key Laboratory of Bioreactor Engineering, New World Institute of 
      Biotechnology, East China University of Science and Technology, Shanghai, 
      People's Republic of China.
FAU - Lv, Xinxin
AU  - Lv X
AD  - State Key Laboratory of Bioreactor Engineering, New World Institute of 
      Biotechnology, East China University of Science and Technology, Shanghai, 
      People's Republic of China.
FAU - Wei, Dongzhi
AU  - Wei D
AD  - State Key Laboratory of Bioreactor Engineering, New World Institute of 
      Biotechnology, East China University of Science and Technology, Shanghai, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Interleukins)
RN  - 0 (Oligopeptides)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (interleukin-24)
RN  - 113516-56-6 (lysyl-aspartyl-glutamyl-leucine)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/*physiology
MH  - Cell Line, Tumor
MH  - Endoplasmic Reticulum/*metabolism
MH  - Endoplasmic Reticulum Stress/genetics/*physiology
MH  - Humans
MH  - Interleukins/genetics/*metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasms/metabolism/*pathology
MH  - Oligopeptides/*metabolism
MH  - Protein Sorting Signals
MH  - Recombinant Fusion Proteins/*metabolism
EDAT- 2015/06/03 06:00
MHDA- 2016/01/20 06:00
CRDT- 2015/06/03 06:00
PHST- 2015/01/21 00:00 [received]
PHST- 2015/05/20 00:00 [accepted]
PHST- 2015/06/03 06:00 [entrez]
PHST- 2015/06/03 06:00 [pubmed]
PHST- 2016/01/20 06:00 [medline]
AID - 10.1002/jcp.25054 [doi]
PST - ppublish
SO  - J Cell Physiol. 2016 Jan;231(1):84-93. doi: 10.1002/jcp.25054.