Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway
Daniel Habermehl* 1 , Bernd Kammerer* 2 , René Handrick1 , Therese Eldh1 , Charlotte Gruber1 , Nils Cordes4 , Peter T Daniel5 , Ludwig Plasswilm3 , Michael Bamberg1 , Claus Belka1 and Verena Jendrossek1
CONCLUSION
Taken together, our investigation clearly shows that induction of apoptosis contributes to the cytotoxic effects of the pharmaceutical preparation Ukrain. Ukrain induced apoptosis independently from death receptor signalling via a pathway involving mitochondrial damage and caspase-activation that were partially sensitive to overexpression of Bcl-2, Bcl-xL and a dominant negative caspase-9.
Importantly, our mass spectrometric data reveal that instead of the composition indicated by the manufacturer the pharmaceutical preparation Ukrain constitutes a mixture of Chelidonium majus L. alkaloids including chelidonine, protopine, allocryptopine, chelerythrine and sanguinarine. In addition to native Chelidonium majus L. extract the isolated alkaloids sanguinarine, chelerythrine and chelidonine were identified as potent inducers of apoptosis in Jurkat T-Lymphoma cells that induced cell death with similar potency as Ukrain. Consequently, our data strongly suggest that the observed antineoplastic effects of Ukrain are based on proapoptotic Chelidonium majus L. alkaloids instead of the hypothetic "Ukrain-molecule" and implicate that purified Chelidonium majus L. alkaloids should be considered for further preclinical and clinical development as single drugs or in combination with standard therapies including ionizing radiation.