Anticancer activities of bovine and human lactoferricin-derived peptides.
Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.
a Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.
Mauricio
M
Arias
b Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.|c Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Ashley L
AL
Hilchie
b Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Evan F
EF
Haney
d Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University of Amsterdam, 1081 AL Amsterdam, the Netherlands.
Jan G M
JG
Bolscher
e Department of Surgery, Division of Urology, Southern Alberta Institute of Urology, University of Calgary, Calgary, AB T2V 1P9, Canada.
M Eric
ME
Hyndman
b Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Robert E W
RE
Hancock
a Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.|b Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Hans J
HJ
Vogel
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002417:Cattle; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D007781:Lactoferrin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D010446:Peptide Fragments; C082171:lactoferricin B; D007781:Lactoferrin
anticancer; anticancéreux; breast cancer; cancer du sein; lactoferricin; lactoferricine; lactoferrin; lactoferrine; leucémie; leukemia