Article

Autophagonizer, a novel synthetic small molecule, induces autophagic cell death.

Chemical Genomics Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Biochemical and Biophysical Research Communications (impact factor: 2.48). 02/2010; 393(4):849-54. DOI:10.1016/j.bbrc.2010.02.097 pp.849-54
Source: PubMed

ABSTRACT Autophagy is an apoptosis-independent mechanism of cell death that protects the cell from environmental imbalances and infection by pathogens. We identified a novel small molecule, 2-(3-Benzyl-4-oxo-3,4,5,6,7,8-hexahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-ylsulfanylmethyl)-oxazole-4-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (referred as autophagonizer), using high-content cell-based screening and the autophagosome marker EGFP-LC3. Autophagonizer inhibited growth and induced cell death in the human tumor cell lines MCF7, HeLa, HCT116, A549, AGS, and HT1080 via a caspase-independent pathway. Conversion of cytosolic LC3-I to autophagosome-associated LC3-II was greatly enhanced by autophagonizer treatment. Transmission electron microscopy and acridine orange staining revealed increased autophagy in the cytoplasm of autophagonizer-treated cells. In conclusion, autophagonizer is a novel autophagy inducer with unique structure, which induces autophagic cell death in the human tumor cell lines.

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Keywords

2-(3-Benzyl-4-oxo-3,4,5,6,7,8-hexahydro-benzo[4,5]thieno[2,3-d]pyrimidin-2-ylsulfanylmethyl)-oxazole-4-carboxylic acid
 
acridine orange staining
 
Autophagonizer inhibited growth
 
autophagonizer treatment
 
autophagonizer-treated cells
 
autophagosome marker EGFP-LC3
 
autophagosome-associated LC3-II
 
caspase-independent pathway
 
cell death
 
cytosolic LC3-I
 
environmental imbalances
 
high-content cell-based screening
 
human tumor cell lines
 
human tumor cell lines MCF7
 
induced cell death
 
induces autophagic cell death
 
novel autophagy inducer
 
novel small molecule
 
Transmission electron microscopy
 
unique structure