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Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components

Rath, Emma M.; Duff, Anthony P.; Håkansson, Anders LU ; Vacher, Catherine S.; Liu, Guo Jun; Knott, Robert B. and Church, W. Bret (2015) In Journal of Pharmacy and Pharmaceutical Sciences 18(4). p.773-824
Abstract
The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the... (More)
The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the HAMLET family has been trialled. Multiple cytotoxic mechanisms have been hypothesised for the HAMLET-like compounds, but it is not yet clear which of those are the initiating cytotoxic mechanism(s) and which are subsequent activities triggered by the initiating mechanism(s). In addition to the studies into the structure of these compounds, this review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Pharmacy and Pharmaceutical Sciences
volume
18
issue
4
pages
773 - 824
publisher
Canadian Society for Pharmaceutical Sciences
external identifiers
  • wos:000368900300021
  • scopus:84979782485
ISSN
1482-1826
language
English
LU publication?
no
id
7d163b26-f308-4b60-9c31-db3a1dbf2cf7 (old id 8731878)
alternative location
http://ejournals.library.ualberta.ca/index.php/JPPS/article/view/25205/19193
date added to LUP
2016-03-01 07:15:58
date last changed
2017-11-19 03:45:34
@article{7d163b26-f308-4b60-9c31-db3a1dbf2cf7,
  abstract     = {The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the HAMLET family has been trialled. Multiple cytotoxic mechanisms have been hypothesised for the HAMLET-like compounds, but it is not yet clear which of those are the initiating cytotoxic mechanism(s) and which are subsequent activities triggered by the initiating mechanism(s). In addition to the studies into the structure of these compounds, this review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified.},
  author       = {Rath, Emma M. and Duff, Anthony P. and Håkansson, Anders and Vacher, Catherine S. and Liu, Guo Jun and Knott, Robert B. and Church, W. Bret},
  issn         = {1482-1826},
  language     = {eng},
  number       = {4},
  pages        = {773--824},
  publisher    = {Canadian Society for Pharmaceutical Sciences},
  series       = {Journal of Pharmacy and Pharmaceutical Sciences},
  title        = {Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components},
  volume       = {18},
  year         = {2015},
}