Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa.

Growth inhibitory activities of novel water extracts of Uncaria tomentosa (C-Med-100(TM)) were examined in vitro using two human leukemic cell lines (K562 and HL60) and one human EBV-transformed B lymphoma cell line (Raji). The proliferative capacities of HL60 and Raji cells were strongly suppressed in the presence of the C-Med-100(TM) while K562 was more resistant to the inhibition. Furthermore, antiproliferative effect was confirmed using the clonogenic assay, which showed a very close correlation between C-Med-100(TM) concentration and the surviving fraction. The suppressive effect of Uncaria tomentosa extracts on tumor cell growth appears to be mediated through induction of apoptosis which was demonstrated by characteristic morphological changes, internucleosomal DNA fragmentation after agarose gel electrophoresis and DNA fragmentation quantification. C-Med-100(TM) induced a delayed type of apoptosis becoming most dose-dependently prominent after 48 hours of exposure. Both DNA single and double strand break were increased 24 hours after C-Med-100(TM) treatment which suggested a well-established linkage between the DNA damage and apoptosis. The induction of DNA strand break coupled to apoptosis may explain the growth inhibition of the tumor cells by Uncaria tomentosa extracts. These results provide the first direct evidence for the antitumor properties of Uncaria tomentosa extracts to be via a mechanism of selective induction of apoptosis.