Theranostics 2017; 7(18):4566-4576. doi:10.7150/thno.19840 This issue

Research Paper

In-Tether Chiral Center Induced Helical Peptide Modulators Target p53-MDM2/MDMX and Inhibit Tumor Growth in Stem-Like Cancer Cell

Kuan Hu1*, Feng Yin1*, Mengyin Yu1, Chengjie Sun1, Jingxu Li1, Yujie Liang1, Wenjun Li1, Mingsheng Xie1, Yuanzhi Lao3, Wei Liang2✉, Zi-gang Li1✉

1. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China
2. Department of Radiation Oncology, the First Affiliated Hospital, Anhui Medical University, Hefei, 230022, China
3. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
* These authors contributed equally to this work.

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Citation:
Hu K, Yin F, Yu M, Sun C, Li J, Liang Y, Li W, Xie M, Lao Y, Liang W, Li Zg. In-Tether Chiral Center Induced Helical Peptide Modulators Target p53-MDM2/MDMX and Inhibit Tumor Growth in Stem-Like Cancer Cell. Theranostics 2017; 7(18):4566-4576. doi:10.7150/thno.19840. Available from https://www.thno.org/v07p4566.htm

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Abstract

Graphic abstract

Inhibition of the interaction between p53 and MDM2/MDMX has attracted significant attention in anticancer therapy development. We designed a series of in-tether chiral center-induced helical stabilized peptides, among which MeR/PhR effectively reactivated p53. The activation of p53 inhibits cell proliferation and induces apoptosis in both the MCF-7 normal tumor cell line and the PA-1 pluripotent cancer cell line with only minimal cellular toxicity towards normal cells or cancer cell lines with p53 mutations. The in vivo bioactivity study of the peptide in the ovarian teratocarcinoma (PA-1) xenograft model showed a tumor growth rate inhibition of 70% with a dosage of 10 mg/kg (one injection every other day). This is the first application of a stabilized peptide modulator targeting stem-like cancer cell both in vitro and in vivo and provides references to cancer stem cell therapy.

Keywords: Chirality-induced helical peptide, stem-like cancer cell, Cancer, p53-MDM2/MDMX.