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HAMLET kills tumor cells by apoptosis: Structure, cellular mechanisms, and therapy

Gustafsson, Lotta LU orcid ; Hallgren, Oskar LU ; Mossberg, Anki LU ; Pettersson, Jenny LU ; Fischer, W ; Aronsson, Annika LU and Svanborg, Catharina LU (2005) In Journal of Nutrition 135(5). p.1299-1303
Abstract
New cancer treatments should aim to destroy tumor cells without disturbing normal tissue. HAMLET (human a-lactalbumin made lethal to tumor cells) offers a new molecular approach to solving this problem, because it induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. After partial unfolding and binding to oleic acid, α-lactalbumin forms the HAMLET complex, which enters tumor cells and freezes their metabolic machinery. The cells proceed to fragment their DNA, and they disintegrate with apoptosis-like characteristics. HAMLET kills a wide range of malignant cells in vitro and maintains this activity in vivo in patients with skin papillomas. In addition, HAMLET has striking effects on human glioblastomas in a rat... (More)
New cancer treatments should aim to destroy tumor cells without disturbing normal tissue. HAMLET (human a-lactalbumin made lethal to tumor cells) offers a new molecular approach to solving this problem, because it induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. After partial unfolding and binding to oleic acid, α-lactalbumin forms the HAMLET complex, which enters tumor cells and freezes their metabolic machinery. The cells proceed to fragment their DNA, and they disintegrate with apoptosis-like characteristics. HAMLET kills a wide range of malignant cells in vitro and maintains this activity in vivo in patients with skin papillomas. In addition, HAMLET has striking effects on human glioblastomas in a rat xenograft model. After convection-enhanced delivery, HAMLET diffuses throughout the brain, selectively killing tumor cells and controlling tumor progression without apparent tissue toxicity. HAMLET thus shows great promise as a new therapeutic with the advantage of selectivity for tumor cells and lack of toxicity. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
lactalbumin, human milk, tumor, apoptosis, protein folding
in
Journal of Nutrition
volume
135
issue
5
pages
1299 - 1303
publisher
Oxford University Press
external identifiers
  • wos:000228953600063
  • pmid:15867328
  • scopus:18344368870
ISSN
1541-6100
project
HAMLET- In vivo effects and mechanisms of tumor cells death
language
English
LU publication?
yes
id
b95857f2-7af3-4fa9-b592-98feeabe4208 (old id 240479)
alternative location
http://jn.nutrition.org/cgi/content/full/135/5/1299
date added to LUP
2016-04-01 11:56:09
date last changed
2021-09-22 05:55:35
@article{b95857f2-7af3-4fa9-b592-98feeabe4208,
  abstract     = {New cancer treatments should aim to destroy tumor cells without disturbing normal tissue. HAMLET (human a-lactalbumin made lethal to tumor cells) offers a new molecular approach to solving this problem, because it induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. After partial unfolding and binding to oleic acid, α-lactalbumin forms the HAMLET complex, which enters tumor cells and freezes their metabolic machinery. The cells proceed to fragment their DNA, and they disintegrate with apoptosis-like characteristics. HAMLET kills a wide range of malignant cells in vitro and maintains this activity in vivo in patients with skin papillomas. In addition, HAMLET has striking effects on human glioblastomas in a rat xenograft model. After convection-enhanced delivery, HAMLET diffuses throughout the brain, selectively killing tumor cells and controlling tumor progression without apparent tissue toxicity. HAMLET thus shows great promise as a new therapeutic with the advantage of selectivity for tumor cells and lack of toxicity.},
  author       = {Gustafsson, Lotta and Hallgren, Oskar and Mossberg, Anki and Pettersson, Jenny and Fischer, W and Aronsson, Annika and Svanborg, Catharina},
  issn         = {1541-6100},
  language     = {eng},
  number       = {5},
  pages        = {1299--1303},
  publisher    = {Oxford University Press},
  series       = {Journal of Nutrition},
  title        = {HAMLET kills tumor cells by apoptosis: Structure, cellular mechanisms, and therapy},
  url          = {http://jn.nutrition.org/cgi/content/full/135/5/1299},
  volume       = {135},
  year         = {2005},
}