TASPINE
An alkaloid isolated for the first time by Vaisberg et al. [84] from the bark latex of the plant species :
Croton lechleri Müll. Arg.
Previous in vitro and in vivo investigations have demonstrated that taspine promotes early phases of wound healing in a dose-dependent manner [84, 85].
Taspine was also demonstrated to activate the pro-apoptotic cascade, which oligomerizes Bak/Bax into pores that result in the release of cytochrome c and consequently apoptosis in HCT116 colon carcinoma cells [86].
Similar results were reported for an in vivo study conducted with ZR-75-30 human breast cancer xenografts in athymic mice [87].
The mechanism of action of taspine as a topoisomerase inhibitor was revealed recently.
Initially, using in vitro assays, Fayad et al. [86] observed the inhibition of both topoisomerases I and II by taspine. Castelli et al. [88] corroborated the inhibitory action of taspine on purified topoisomerase I and provided the molecular details of the inhibitory action.
These researchers showed that taspine inhibits the catalytic process (cleavage and religation), and molecular docking simulations showed that the formation of the complex enzyme-taspine is accomplished by the interaction in the proximity of the active site preventing the cleavage reaction. While, that the religation inhibition is explained by DNA intercalation of the inhibitor with the enzyme-DNA-binary complex.
Croton lechleri Müll. Arg.
Previous in vitro and in vivo investigations have demonstrated that taspine promotes early phases of wound healing in a dose-dependent manner [84, 85].
Taspine was also demonstrated to activate the pro-apoptotic cascade, which oligomerizes Bak/Bax into pores that result in the release of cytochrome c and consequently apoptosis in HCT116 colon carcinoma cells [86].
Similar results were reported for an in vivo study conducted with ZR-75-30 human breast cancer xenografts in athymic mice [87].
The mechanism of action of taspine as a topoisomerase inhibitor was revealed recently.
Initially, using in vitro assays, Fayad et al. [86] observed the inhibition of both topoisomerases I and II by taspine. Castelli et al. [88] corroborated the inhibitory action of taspine on purified topoisomerase I and provided the molecular details of the inhibitory action.
These researchers showed that taspine inhibits the catalytic process (cleavage and religation), and molecular docking simulations showed that the formation of the complex enzyme-taspine is accomplished by the interaction in the proximity of the active site preventing the cleavage reaction. While, that the religation inhibition is explained by DNA intercalation of the inhibitor with the enzyme-DNA-binary complex.
