The novel proapoptotic activity of nonnatural enantiomer of Lentiginosine

被引:44
作者
Macchi, Beatrice [1 ,2 ]
Minutolo, Antonella [3 ]
Grelli, Sandro [3 ]
Cardona, Francesca [4 ]
Cordero, Franca M. [4 ]
Mastino, Antonio [5 ,6 ]
Brandi, Alberto [4 ]
机构
[1] Univ Roma Tor Vergata, Dept Neurosci, I-00133 Rome, Italy
[2] IRCCS S Lucia, I-00100 Rome, Italy
[3] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy
[4] Univ Florence, Dept Organ Chem, Ugo Shiff & HeteroBioLab, I-50019 Sesto Fiorentino, FI, Italy
[5] Univ Messina, Dept Life Sci, I-98168 Messina, Italy
[6] Univ Messina, IRCCS, Ctr Neurolesi Bonino Pulejo, I-98168 Messina, Italy
关键词
apoptosis; cytotoxicity; iminosugars; indolizidine alkaloids; lentiginosine; NATURAL OCCURRENCE; CANCER; INHIBITOR; (+)-LENTIGINOSINE; CASTANOSPERMINE; GLYCOSYLATION; SWAINSONINE;
D O I
10.1093/glycob/cwp202
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:500 / 506
页数:7
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