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). T he 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 c lonogenic assay, which showed a very close correlation between C-Med-100(TM ) concentration and the surviving fraction. The suppressive effect of Uncar ia tomentosa extracts on tumor cell growth appears to be mediated through i nduction of apoptosis which was demonstrated by characteristic morphologica l changes, internucleosomal DNA fragmentation after agarose gel electrophor esis and DNA fragmentation quantification. C-Med-100(TM) induced a delayed type of apoptosis becoming most dose-dependently prominent after 48 hours o f exposure. Both DNA single and double strand break were increased 24 hours after C-Med-100(TM) treatment which suggested a well-established linkage b etween the DNA damage and apoptosis. The induction of DNA strand break coup led to apoptosis may explain the growth inhibition of the tumor cells by Un caria tomentosa extracts. These results provide the first direct evidence f or the antitumor properties of Uncaria tomentosa extracts to be via a mecha nism of selective induction of apoptosis.