PMID- 30108906
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230928
IS  - 2040-2503 (Print)
IS  - 2040-2511 (Electronic)
IS  - 2040-2503 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Jan 1
TI  - Novel cell-penetrating-amyloid peptide conjugates preferentially kill cancer 
      cells.
PG  - 121-130
LID - 10.1039/c7md00321h [doi]
AB  - The goal of this study was to develop a peptide which could use the toxic effects 
      of amyloid, a substance which is the hallmark of over 25 known human diseases, to 
      selectively kill cancer cells. Here we demonstrate that two separate 
      amyloid-forming hexapeptides, one from the microtubule associated protein Tau 
      involved in formation of paired helical filaments of Alzheimer's disease, and the 
      other an amyloid forming sequence from apolipoprotein A(1), when conjugated to a 
      cell penetrating peptide (CPP) sequence, form toxic oligomers which are stable 
      for up to 14 h and able to enter cells by a combination of endocytosis and 
      transduction. The amyloid peptide conjugates showed selective cytotoxicity to 
      breast cancer, neuroblastoma and cervical cancer cells in culture compared to 
      normal cells. Fluorescence imaging experiments showed the CPP-amyloid peptide 
      oligomers formed intracellular fibrous amyloid, visible in the 
      endosomes/lysosomes, cytosol and nucleus with thioflavin S (ThS) staining. 
      Further experiments with rhodamine-conjugated Dextran, propidium iodide (PI), and 
      acridine orange (AO) suggested the mechanism of cell death was the permeability 
      of the lysosomal membrane brought about by the formation of amyloid pores. 
      Cytotoxicity could be abrogated by inhibitors of lysosomal hydrolases, consistent 
      with a model where lysosomal hydrolases leak into the cytosol and induce 
      cytotoxicity in subsequent downstream steps. Taken together, our data suggest 
      that CPP-amyloid peptide conjugates show potential as a new class of anti-cancer 
      peptides (ACPs).
FAU - Veloria, John R
AU  - Veloria JR
AUID- ORCID: 0000-0003-2024-2245
AD  - Department of Biological Sciences , The University of Texas at Dallas , 800 W. 
      Campbell Rd , Richardson , TX 75080 , USA.
FAU - Chen, Luxi
AU  - Chen L
AD  - Department of Chemistry and Biochemistry , The University of Texas at Dallas , 
      800 W. Campbell Rd , Richardson , TX 75080 , USA . Email: wgoux@utdallas.edu.
FAU - Li, Lin
AU  - Li L
AD  - Department of Biological Sciences , The University of Texas at Dallas , 800 W. 
      Campbell Rd , Richardson , TX 75080 , USA.
FAU - Breen, Gail A M
AU  - Breen GAM
AD  - Department of Biological Sciences , The University of Texas at Dallas , 800 W. 
      Campbell Rd , Richardson , TX 75080 , USA.
FAU - Lee, Jiyong
AU  - Lee J
AD  - Department of Chemistry and Biochemistry , The University of Texas at Dallas , 
      800 W. Campbell Rd , Richardson , TX 75080 , USA . Email: wgoux@utdallas.edu.
FAU - Goux, Warren J
AU  - Goux WJ
AUID- ORCID: 0000-0002-3697-6289
AD  - Department of Chemistry and Biochemistry , The University of Texas at Dallas , 
      800 W. Campbell Rd , Richardson , TX 75080 , USA . Email: wgoux@utdallas.edu.
LA  - eng
PT  - Journal Article
DEP - 20171205
PL  - England
TA  - Medchemcomm
JT  - MedChemComm
JID - 101531525
PMC - PMC6071918
EDAT- 2018/08/16 06:00
MHDA- 2018/08/16 06:01
PMCR- 2018/12/05
CRDT- 2018/08/16 06:00
PHST- 2017/06/26 00:00 [received]
PHST- 2017/09/09 00:00 [accepted]
PHST- 2018/08/16 06:00 [entrez]
PHST- 2018/08/16 06:00 [pubmed]
PHST- 2018/08/16 06:01 [medline]
PHST- 2018/12/05 00:00 [pmc-release]
AID - c7md00321h [pii]
AID - 10.1039/c7md00321h [doi]
PST - epublish
SO  - Medchemcomm. 2017 Dec 5;9(1):121-130. doi: 10.1039/c7md00321h. eCollection 2018 
      Jan 1.