Apoptosis-inducing activity of Helleborus niger in ALL and AML.
BACKGROUND
Helleborus niger is used in the adjuvant treatment of different tumors in anthroposophical medicine. Indications include various types of brain tumors in children, as well as prostate cancer, leukemia and lymphoma. Our aim was to investigate the therapeutic effects of these extracts apart from the traditional use.


METHODS
: We used an aqueous whole plant extract of H. niger in different cancer and leukemia cell lines and primary cells of patients with childhood ALL and AML and identified the main mechanisms of action.


RESULTS
A strong inhibition of proliferation is caused by specific apoptosis induction, which is executed via the mitochondrial pathway and caspase-3 processing. Apoptosis could be detected in lymphoma (BJAB), leukemia (Reh, Nalm6, Sup-B15) and melanoma (Mel-HO) cells and overcomes a Bcl-2-mediated block of apoptosis. In primary cells of patients with childhood ALL and AML, which were partly poor responding to doxorubicin and daunorubicin, a strong apoptosis induction was determined. In combination with the vinca alkaloid vincristine, strong synergistic effects were detected in BJAB cells.


CONCLUSIONS
We demonstrate in vitro efficacy of H. niger extract in cells of hematological malignancies; these studies should encourage in vivo experiments.
Jesse
Patrick
P
Department of Pediatric Oncology/Hematology, Charité, Universitätsmedizin Berlin, Berlin, Germany. patrick.jesse@charite.de
Mottke
Gritt
G
Eberle
Jürgen
J
Seifert
Georg
G
Henze
Günter
G
Prokop
Aram
A
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D004357:Drug Synergism; D039322:Helleborus / Q000737:chemistry*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D010936:Plant Extracts; D053148:Caspase 3