Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells)

Advances in Experimental Medicine and Biology
Oskar HallgrenCatharina Svanborg

Abstract

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity intera...Continue Reading

Citations

Sep 27, 2008·The Journal of Biological Chemistry·Nicolas Smadja-LamèreJosée N Lavoie
Aug 16, 2011·Critical Reviews in Food Science and Nutrition·Chockry BarbanaMaría D Pérez
Sep 18, 2012·Virology Journal·Esmail M El-FakharanyElrashdy M Redwan
Jan 16, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Aline do Carmo França-BotelhoAdenilda Cristina Honório-França
Nov 17, 2016·Revista da Associação Médica Brasileira·Patricia Palmeira, Magda Carneiro-Sampaio
Oct 20, 2009·European Journal of Pharmacology·Mathieu H M Noteborn
Apr 28, 2011·Experimental Biology and Medicine·Konstantinos ArgirisMahvash Tavassoli
Aug 4, 2009·Journal of Mammary Gland Biology and Neoplasia·Margaret C Neville
Mar 20, 2010·Stem Cell Reviews and Reports·Sergey V AnisimovAna S Correia
Oct 12, 2010·Oncogene·V PavetH Gronemeyer
Oct 28, 2010·The FEBS Journal·Ann-Kristin MossbergCatharina Svanborg
Nov 12, 2014·Biochemistry. Biokhimii︠a︡·A A RosenkranzA S Sobolev
Sep 10, 2016·PloS One·Ganapathy Narmadha, Suresh Yenugu
Mar 10, 2015·Biochemistry. Biokhimii︠a︡·V E BychkovaV A Balobanov
Jan 8, 2010·Molecular Cancer Therapeutics·Paul RammerMarja Jäättelä

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