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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8731878
- author
- Rath, Emma M.
; Duff, Anthony P.
; Håkansson, Anders
LU
; Vacher, Catherine S.
; Liu, Guo Jun
; Knott, Robert B.
and Church, W. Bret
- organization
- publishing date
- 2015
- 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?
- yes
- 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
- 2016-04-01 13:22:58
- date last changed
- 2022-02-04 03:59:00
@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}},
url = {{http://ejournals.library.ualberta.ca/index.php/JPPS/article/view/25205/19193}},
volume = {{18}},
year = {{2015}},
}