Apoptosis of human leukemia cells induced by artepillin C, an active ingredient of Brazilian propolis

Artepillin C (3, 5-diprenyl-4-hydroxycinnamic acid) is an active ingredient of Brazilian propolis that possesses anti-tumor activity. When Artepillin C was applied to human leukemia cell lines of different phenotypes, namely, lymphocytic leukemia (7 cell lines of T-cell, 5 cell lines of B-cell), mye loid and monocytic leukemia and non-lymphoid non-myeloid leukemia cell line s in vitro, Artepillin C exhibited potent cytocidal effects and induced mar ked levels of apoptosis in all the cell lines. The most potent effects were observed in the T-cell lines. Apoptotic bodies and DNA fragmentation were induced in the cell lines after exposure to Artepillin C. DNA synthesis in the leukemia cells M,ns clearly inhibited and disintegration of the cells w as confirmed microscopically. Apoptosis of the leukemia cells may be partia lly associated with enhanced Fas antigen expression and loss of mitochondri al membrane potential. In contrast, although Artepillin C inhibited the gro wth of pokeweed mitogen (PWM)-stimulated normal blood lymphocytes, it was n ot cytocidal to normal unstimulated lymphocytes. These results suggested th at Artepillin C, an active ingredient of Brazilian propolis, has anti-leuke mic effects with limited inhibitory effects on normal lymphocytes.