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.
Macchi, B., Minutolo, A., Grelli, S., Cardona, F., Cordero, F., Mastino, A., et al. (2010). The novel proapoptotic activity of nonnatural enantiomer of Lentiginosine. GLYCOBIOLOGY, 30(5), 500-506 [10.1093/glycob/cwp202].
The novel proapoptotic activity of nonnatural enantiomer of Lentiginosine
MACCHI, BEATRICE;Minutolo, A;GRELLI, SANDRO;
2010-01-01
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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