ELAS1 induces apoptotic death in adenocarcinoma DU145 and squamous-cell carcinoma SAS cancer cells, but not in normal KD cells
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Toshihiro Uchihashi1,*, Kaori Ota2,*, Yusuke Yabuno1,*, Shouichi Ohno2, Kohshiro Fukushima2, Yoko Naito2, Mikihiko Kogo1, Norikazu Yabuta2,** and Hiroshi Nojima2
1First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan
2Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
*These authors have contributed equally to this work
**Corresponding author for cell biological experiments
Norikazu Yabuta, email: [email protected]
Hiroshi Nojima, email: [email protected]
Keywords: cyclin G1, p53, DU145, SAS, adenovirus
Received: December 14, 2016 Accepted: May 03, 2017 Published: August 24, 2017
We previously reported that an ELAS1 peptide containing 29 amino acids induces apoptotic death in U2OS human osteosarcoma cells following DNA double-strand break insults. Here, we show that ELAS1 also caused apoptosis in prostate adenocarcinoma DU145 cells and tongue squamous-cell carcinoma SAS cells. ELAS1 appears to be safe because it induced apoptosis only in cancer cells, not in normal KD cells. Because the effect of ELAS1 is dependent on increased stability of p53 and enhanced phosphorylation of p53-S46, we exogenously expressed wild-type p53 protein to fully promote ELAS1-mediated induction of apoptosis in SAS cells. Interestingly, simultaneous expression of Myc-ELAS1 and FLAG-p53 mediated by an internal ribosome entry site efficiently induced apoptosis in SAS cells. Moreover, we prepared a recombinant adenovirus that simultaneously expressed Myc-ELAS1 and FLAG-p53. This adenovirus also killed SAS cells, as determined by a cell viability assay, in the presence of camptothecin, an inducer of DNA double-strand breaks. Moreover, nude mice harboring Myc-ELAS1-expressing SAS cells lived longer than mice harboring Myc-vector-expressing SAS cells, suggesting the usefulness of ELAS1 in vivo. Notably, Cy5-tagged ELAS1-t, which contained only ten amino acids, also efficiently induced apoptosis in both DU145 and SAS cells, suggesting the usefulness of ELAS1-t as a peptide. Taken together, our results suggest that ELAS1 is therapeutically useful as a peptide drug.
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