An antimicrobial peptide containing NGR motif has potent antitumor activity against CD13+ and CD13- tumor cells.

Abstract

Antimicrobial peptides (AMPs) with Asn-Gly-Arg (NGR) motif have potent cytotoxicity, preferably against tumor cells due to their binding to CD13 on tumor cells. However, the importance of αvβ3 expression for antitumor activity of AMPs containing NGR has not been clarified. This study was aimed at designing a new AMP containing NGR and testing their biological activity against different types of tumor cells with varying CD13 and αvβ3 expression. We first synthesized the new AMP containing NGR motif (CK21), which effectively entered into CD13+ HT-1080, but less into CD13- αvβ3+ MDA-MB-435 and further less into stable αvβ3-silencing MDA-MB-435 cells. Furthermore, CK21 displayed dose-dependent antiproliferation against these tumor cells and induced cell cycling arrest at G2/M phases and apoptosis of these tumor cells. In addition, CK21 inhibited the invasion of these tumor cells in vitro and inhibited the growth of implanted tumor cells in vivo. Particularly, the antitumor effect of CK21 in CD13+ HT-1080 was stronger than that of CD13- αvβ3+ MDA-MB-435 and much stronger than that of stable αvβ3-silencing MDA-MB-435. Our data indicated that the new AMPs containing NGR had potent antitumor activity against CD13+ or αvβ3+ tumor cells, preferably against CD13+ tumor cells, possibly through binding to CD13 or αvβ3 on tumor cells.

• Authors: Zhe Zhang, Lei Hou, Lu Feng, Shangke Huang, Minna Luo, Shan Shao, Xiaojin Zhang, Shanzhi Gu, Xinhan Zhao
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 10 Pg. 8167-75 (Sep 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25990455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• NGR peptide
• Oligopeptides
• Peptide Fragments
• CD13 Antigens

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• CD13 Antigens (metabolism)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Flow Cytometry
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms (drug therapy, metabolism, pathology)
• Oligopeptides (pharmacology)
• Peptide Fragments (pharmacology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays