3 years ago

Polymer–KLAK Peptide Conjugates Induce Cancer Cell Death through Synergistic Effects of Mitochondria Damage and Autophagy Blockage

Polymer–KLAK Peptide Conjugates Induce Cancer Cell Death through Synergistic Effects of Mitochondria Damage and Autophagy Blockage
Hao Wang, Dan Li, Xiao-Hui Nan, Yi Wang, Qiao-Jun Fang, Zeng-Ying Qiao, Wen-Jia Lai, Yao-Xin Lin
Nanoscaled polymer–peptide conjugates (PPCs) containing both functional peptides and synthetic polymer comprise a new family of biomaterials that can circumvent the limitation of peptides alone. Our previous work showed that PPCs with the therapeutic peptide KLAK, especially PPCs with shorter PEG spacers and a higher degree of polymerization, exhibit enhanced antitumor effects through disrupting mitochondrial membranes. However, as PPCs have a spherical nanostructure (45–60 nm), this may have other effects besides the conjugated therapeutic peptide KLAK itself when they enter cancer cells. In this research, we compared the proteome differences of U87 cells treated with KLAK, polymer, and their conjugates (PKLAK) through quantitative proteomics technology. The result reveals that proteins involved in oxidative stress response and the Nrf2/ARE pathway were significantly up-regulated after PKLAK treatment. Moreover, the overexpression of sequestosome 1, a protein substrate that is selectively incorporated into the formation of autophagosome and degraded by autophagy, is found in our study and has not been reported previously in the study of KLAK toxicity. Additional experiments suggest that upon endocytosis, PKLAK causes lysosome impairment and results in autophagosomes accumulation. Hence, PKLAK might induce U87 cell death by autophagy blockage due to lysosome impairment as well as mitochondria damage synergistically.

Publisher URL: http://dx.doi.org/10.1021/acs.bioconjchem.7b00176

DOI: 10.1021/acs.bioconjchem.7b00176

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.