title: Synthetic menthyl α/β-(1→6)-diglucopyranosides-induced cell death in human leukemia cells is dependent on caspases.
abstract: A series of alkyl α/β-(1→6)-diglucopyranosides 1-12 were synthesized and assessed for cytotoxicity against HL-60, U937, Molt-3 and MCF-7 cancer cell lines. The menthyl derivatives displayed strong cytotoxic properties showing IC(50) values between 6 and 16 μM. Furthermore, we demonstrated that the selected synthetic (+)-menthyl β-(1→6)-diglucopyranoside 5 induces apoptotic cell death in human leukemia cells through a mechanism that involves activation of multiple caspases. Cell death was completely prevented by the non-specific caspase inhibitor z-VAD-fmk and found to be associated with the release of cytochrome c, an increase in the expression of Bax levels and a decrease in the generation of reactive oxygen species.
authors.affiliation: Departamento de Bioquímica, Unidad Asociada al Consejo Superior de Investigaciones Científicas, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Marrero
authors.forename: Sara
authors.initials: S
authors.lastname: Tejera
authors.forename: Sara
authors.initials: S
authors.lastname: Estévez
authors.forename: José
authors.initials: J
authors.lastname: Quintana
authors.forename: Carlos
authors.initials: C
authors.lastname: Mayato
authors.forename: Rosa L
authors.initials: RL
authors.lastname: Dorta
authors.forename: Jesús T
authors.initials: JT
authors.lastname: Vázquez
authors.forename: Francisco
authors.initials: F
authors.lastname: Estévez
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D004187:Disaccharides; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045304:Cytochromes c; D020169:Caspases