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HAMLET – A protein-lipid complex with broad tumoricidal activity

Ho, James C S; Nadeem, Aftab LU and Svanborg, Catharina LU (2017) In Biochemical and Biophysical Research Communications 482(3). p.454-458
Abstract

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process. In subsequent studies, we have identified a sequence of interactions that starts with the membrane integration of HAMLET and the activation of ion fluxes followed by HAMLET... (More)

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process. In subsequent studies, we have identified a sequence of interactions that starts with the membrane integration of HAMLET and the activation of ion fluxes followed by HAMLET internalization, progressive inhibition of MAPK kinases and GTPases and sorting of HAMLET to different cellular compartments, including the nuclei. Therapeutic efficacy of HAMLET has been demonstrated in animal models of glioblastoma, bladder cancer and intestinal cancer. In clinical studies, HAMLET has been shown to target skin papillomas and bladder cancers. The findings identify HAMLET as a new drug candidate with promising selectivity for cancer cells and a strong therapeutic potential.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer, Cell death, HAMLET, Ion flux, Membrane, Oncogene
in
Biochemical and Biophysical Research Communications
volume
482
issue
3
pages
5 pages
publisher
Elsevier
external identifiers
  • scopus:85012913916
  • wos:000393270000012
ISSN
0006-291X
DOI
10.1016/j.bbrc.2016.10.092
language
English
LU publication?
yes
id
59a16ae6-bf68-40ee-98c2-7029162c9609
date added to LUP
2017-02-28 11:16:51
date last changed
2018-01-07 11:53:06
@article{59a16ae6-bf68-40ee-98c2-7029162c9609,
  abstract     = {<p>HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process. In subsequent studies, we have identified a sequence of interactions that starts with the membrane integration of HAMLET and the activation of ion fluxes followed by HAMLET internalization, progressive inhibition of MAPK kinases and GTPases and sorting of HAMLET to different cellular compartments, including the nuclei. Therapeutic efficacy of HAMLET has been demonstrated in animal models of glioblastoma, bladder cancer and intestinal cancer. In clinical studies, HAMLET has been shown to target skin papillomas and bladder cancers. The findings identify HAMLET as a new drug candidate with promising selectivity for cancer cells and a strong therapeutic potential.</p>},
  author       = {Ho, James C S and Nadeem, Aftab and Svanborg, Catharina},
  issn         = {0006-291X},
  keyword      = {Cancer,Cell death,HAMLET,Ion flux,Membrane,Oncogene},
  language     = {eng},
  month        = {01},
  number       = {3},
  pages        = {454--458},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {HAMLET – A protein-lipid complex with broad tumoricidal activity},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2016.10.092},
  volume       = {482},
  year         = {2017},
}