D-(−)-Lentiginosine [(−)-4], the nonnatural enantiomer of the iminosugar indolizidine alkaloid L-(+)-lentiginosine, acts as apoptosis inducer on tumor cells of different origin, in contrast to its natural enantiomer. Although D-(−)-4 exhibited a proapoptotic activity towards tumor cells at level lower than the chemotherapeutic agent, SN38, it was less proapoptotic towards normal cells and less cytotoxic. Apoptosis induced by D-(−)-4 was caspase-dependent, as shown by the increased expression and activity of caspase- 3 and -8 in treated cells, and by inhibition following treatment with the pan caspase inhibitor, ZVAD-FMK. This study highlighted how a natural iminosugar alkaloid and its synthetic enantiomer, which were simply known for their inhibition against a fungal glucoamylase, could behave in a complete different way when tested towards cell growth and death of cells of different origin.
The novel proapoptotic activity of nonnatural enantiomer of Lentiginosine / B. Macchi; A. Minutolo; S. Grelli; A. Mastino; F. Cardona; F. M. Cordero; A. Brandi;. - In: GLYCOBIOLOGY. - ISSN 0959-6658. - STAMPA. - 20:(2010), pp. 500-506. [10.1093/glycob/cwp202]
The novel proapoptotic activity of nonnatural enantiomer of Lentiginosine
CARDONA, FRANCESCA;CORDERO, FRANCA MARIA;BRANDI, ALBERTO
2010
Abstract
D-(−)-Lentiginosine [(−)-4], the nonnatural enantiomer of the iminosugar indolizidine alkaloid L-(+)-lentiginosine, acts as apoptosis inducer on tumor cells of different origin, in contrast to its natural enantiomer. Although D-(−)-4 exhibited a proapoptotic activity towards tumor cells at level lower than the chemotherapeutic agent, SN38, it was less proapoptotic towards normal cells and less cytotoxic. Apoptosis induced by D-(−)-4 was caspase-dependent, as shown by the increased expression and activity of caspase- 3 and -8 in treated cells, and by inhibition following treatment with the pan caspase inhibitor, ZVAD-FMK. This study highlighted how a natural iminosugar alkaloid and its synthetic enantiomer, which were simply known for their inhibition against a fungal glucoamylase, could behave in a complete different way when tested towards cell growth and death of cells of different origin.File | Dimensione | Formato | |
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