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), myeloid and monocytic leukemia and non-lymphoid non-myeloid leukemia cell lines in vitro, Artepillin C exhibited potent cytocidal effects and induced marked 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 was clearly inhibited and disintegration of the cells was confirmed microscopically. Apoptosis of the leukemia cells may be partially associated with enhanced Fas antigen expression and loss of mitochondrial membrane potential. In contrast, although Artepillin C inhibited the growth of pokeweed mitogen (PWM)-stimulated normal blood lymphocytes, it was not cytocidal to normal unstimulated lymphocytes. These results suggested that Artepillin C, an active ingredient of Brazilian propolis, has anti-leukemic effects with limited inhibitory effects on normal lymphocytes.
Kimoto
T
T
Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Fujisaki 675-1, Okayama 702-8006, Japan. fujisaki@hayashibara.co.jp
Aga
M
M
Hino
K
K
Koya-Miyata
S
S
Yamamoto
Y
Y
Micallef
M J
MJ
Hanaya
T
T
Arai
S
S
Ikeda
M
M
Kurimoto
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001938:Brazil; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002467:Cell Nucleus / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008519:Medicine, Traditional; D010666:Phenylpropionates / Q000494:pharmacology*; D011429:Propolis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; D010666:Phenylpropionates; D019014:fas Receptor; C102259:artepillin C; D011429:Propolis