title: Effect of ajoene, a natural antitumor small molecule, on human 20S proteasome activity in vitro and in human leukemic HL60 cells.
abstract: The pharmacologic properties of ajoene, the major sulfur-containing compound purified from garlic, and its possible role in the prevention and treatment of cancer has received increasing attention. Several studies demonstrated that induction of apoptosis and cell cycle blockade are typical biologic effects observed in tumor cells after proteasome inhibition. The proteasome is responsible for the degradation of a variety of intracellular proteins and plays a key role in the regulation of many cellular processes. The aim of the present work was therefore to explore the effects of ajoene on the proteasome activities. In vitro activities of 20S proteasome purified from human erythrocytes on fluorogenic peptide substrates specific for trypsin-like, chymotrypsin-like and peptidylglutamyl peptide hydrolyzing activities revealed that ajoene inhibited the trypsin-like activity in a dose- and time-dependent manner. Further, the ability of 20S proteasome to degrade the OVA(51-71) peptide, a model proteasomal substrate, was partially but significantly inhibited by ajoene. In addition, when human leukemia cell line HL60 was treated with ajoene, both trypsin- and chymotrypsin-like activities were affected, cells arrested in G2/M phase and total amount of cytosolic proteasome increased. All these data clearly indicate that ajoene may affect proteasome function and activity both in vitro and in the living cell. This is a novel aspect in the biologic profile of this garlic compound giving new insights into the understanding of the molecular mechanisms of its potential antitumor action.
authors.affiliation: Centre de Recherche en Pharmacologie Santé, UMR 2587 CNRS-Pierre Fabre, 205 route de Narbonne, 31400 Toulouse, France.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: Bernard
authors.initials: B
authors.lastname: Monsarrat
authors.forename: Jean Edouard
authors.initials: JE
authors.lastname: Gairin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Girbal-Neuhauser
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002918:Chymotrypsin / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D005737:Garlic / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D006825:Hybridomas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D061988:Proteasome Inhibitors; D013454:Sulfoxides; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D004791:Enzyme Inhibitors; D010455:Peptides; D010936:Plant Extracts; D061988:Proteasome Inhibitors; D013454:Sulfoxides; C067713:lactacystin; D010047:Ovalbumin; C048980:ajoene; D002918:Chymotrypsin; D014357:Trypsin; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine