Intracellular delivery of bovine lactoferricin's antimicrobial core (RRWQWR) kills T-leukemia cells

Angela Richardson; Roberto de Antueno; Roy Duncan; David W. Hoskin

doi:10.1016/j.bbrc.2009.08.083

Intracellular delivery of bovine lactoferricin's antimicrobial core (RRWQWR) kills T-leukemia cells

Angela Richardson, Roberto de Antueno, Roy Duncan, David W. Hoskin

Research output: Contribution to journal › Article › peer-review

58 Citations (Scopus)

Abstract

Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide with potent cytotoxic activity against cancer cells. The antimicrobial activity of LfcinB resides in its RRWQWR amino acid sequence (referred to here as LfcinB6); however, the anticancer activity of LfcinB6 is not known. Here, we show that free LfcinB6 did not kill T-leukemia or breast cancer cells but LfcinB6 was strongly cytotoxic when delivered to the cytosolic compartment by fusogenic liposomes. LfcinB6 bound weakly to isolated mitochondria but, unlike LfcinB, did not permeabilize mitochondria or cause cytochrome c to be released. Cathepsin B and caspase activity were important for cytotoxicity caused by intracellular LfcinB6 whereas reactive oxygen species were not involved. The mechanism of LfcinB6-induced cytotoxicity is therefore different from that of LfcinB. We suggest that LfcinB6, in combination with a fusogenic liposome delivery system that selectively targets malignant cells, has potential as a novel anticancer agent.

Original language	English
Pages (from-to)	736-741
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	388
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2009.08.083
Publication status	Published - Oct 30 2009

Bibliographical note

Funding Information:
A. Richardson was supported by a Trainee Award from the Cancer Research Training Program with funding from the Canadian Cancer Society. This work was supported by a grant to D. Hoskin from the Leukemia and Lymphoma Society of Canada and to R. Duncan from the Canadian Institutes of Health Research.

ASJC Scopus Subject Areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2009.08.083

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title = "Intracellular delivery of bovine lactoferricin's antimicrobial core (RRWQWR) kills T-leukemia cells",

abstract = "Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide with potent cytotoxic activity against cancer cells. The antimicrobial activity of LfcinB resides in its RRWQWR amino acid sequence (referred to here as LfcinB6); however, the anticancer activity of LfcinB6 is not known. Here, we show that free LfcinB6 did not kill T-leukemia or breast cancer cells but LfcinB6 was strongly cytotoxic when delivered to the cytosolic compartment by fusogenic liposomes. LfcinB6 bound weakly to isolated mitochondria but, unlike LfcinB, did not permeabilize mitochondria or cause cytochrome c to be released. Cathepsin B and caspase activity were important for cytotoxicity caused by intracellular LfcinB6 whereas reactive oxygen species were not involved. The mechanism of LfcinB6-induced cytotoxicity is therefore different from that of LfcinB. We suggest that LfcinB6, in combination with a fusogenic liposome delivery system that selectively targets malignant cells, has potential as a novel anticancer agent.",

author = "Angela Richardson and {de Antueno}, Roberto and Roy Duncan and Hoskin, {David W.}",

note = "Funding Information: A. Richardson was supported by a Trainee Award from the Cancer Research Training Program with funding from the Canadian Cancer Society. This work was supported by a grant to D. Hoskin from the Leukemia and Lymphoma Society of Canada and to R. Duncan from the Canadian Institutes of Health Research.",

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PY - 2009/10/30

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N2 - Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide with potent cytotoxic activity against cancer cells. The antimicrobial activity of LfcinB resides in its RRWQWR amino acid sequence (referred to here as LfcinB6); however, the anticancer activity of LfcinB6 is not known. Here, we show that free LfcinB6 did not kill T-leukemia or breast cancer cells but LfcinB6 was strongly cytotoxic when delivered to the cytosolic compartment by fusogenic liposomes. LfcinB6 bound weakly to isolated mitochondria but, unlike LfcinB, did not permeabilize mitochondria or cause cytochrome c to be released. Cathepsin B and caspase activity were important for cytotoxicity caused by intracellular LfcinB6 whereas reactive oxygen species were not involved. The mechanism of LfcinB6-induced cytotoxicity is therefore different from that of LfcinB. We suggest that LfcinB6, in combination with a fusogenic liposome delivery system that selectively targets malignant cells, has potential as a novel anticancer agent.

AB - Bovine lactoferricin (LfcinB) is a cationic antimicrobial peptide with potent cytotoxic activity against cancer cells. The antimicrobial activity of LfcinB resides in its RRWQWR amino acid sequence (referred to here as LfcinB6); however, the anticancer activity of LfcinB6 is not known. Here, we show that free LfcinB6 did not kill T-leukemia or breast cancer cells but LfcinB6 was strongly cytotoxic when delivered to the cytosolic compartment by fusogenic liposomes. LfcinB6 bound weakly to isolated mitochondria but, unlike LfcinB, did not permeabilize mitochondria or cause cytochrome c to be released. Cathepsin B and caspase activity were important for cytotoxicity caused by intracellular LfcinB6 whereas reactive oxygen species were not involved. The mechanism of LfcinB6-induced cytotoxicity is therefore different from that of LfcinB. We suggest that LfcinB6, in combination with a fusogenic liposome delivery system that selectively targets malignant cells, has potential as a novel anticancer agent.

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Intracellular delivery of bovine lactoferricin's antimicrobial core (RRWQWR) kills T-leukemia cells

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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