HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

Aits, Sonja (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Gustafsson, Lotta (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Hallgren, Oskar (author): Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Lungbiologi,Airway Inflammation and Immunology,Lund University Research Groups,Lung Biology

Brest, Patrick (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Gustafsson, Mattias (author): Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine

Trulsson, Maria (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Mossberg, Anki (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Simon, Hans-Uwe (author)

Mograbi, Baharia (author)

Svanborg, Catharina (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

(creator_code:org_t)

Wiley, 2009
2009
English.
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:5, s. 1008-1019

Related links:: http://www.ncbi.nlm....; show more...; http://dx.doi.org/10...; https://onlinelibrar...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

By the author/editor: Aits, Sonja; Gustafsson, Lott ...; Hallgren, Oskar; Brest, Patrick; Gustafsson, Matt ...; Trulsson, Maria; show more...; Mossberg, Anki; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Cathar ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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