Induction of microtubule-damage, mitotic arrest, Bcl-2 phosphorylation, Bak activation, and mitochondria-dependent caspase cascade is involved in human Jurkat T-cell apoptosis by aruncin B from Aruncus dioicus var. kamtschaticus

Exposure of human Jurkat T cells to aruncin B, purified from Aruncus dioicus, caused apoptosis along with microtubule damage, G2/M-arrest, Bcl-2 phosphorylation, Bak activation, mitochondrial membrane potential (Δψm) loss, cytochrome c release, activation of multiple caspases, and PARP degradation. Analyses by employing Bcl-2 overexpression and selective caspase inhibitors revealed that G2/M-arrest and Bcl-2 phosphorylation occurred prior to mitochondria-dependent activation of caspase-9, -3, and -8. The IC50 values for human resting T cells, activated T cells, and Jurkat T cells were >60 μg/ml, 49 μg/ml, and 22 μg/ml, respectively. These results demonstrate the apoptogenic activity of a novel microtubule-damaging agent aruncin B.