Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells.
We found that bufalin, an active principle of the Chinese medicine chan'su, has selective inhibitory effects on the growth of various human cancer cells. In order to examine whether the growth-inhibitory effect of bufalin on human cancer cells is associated with apoptosis, human leukemia cells were treated with bufalin. HL-60, ML1, and U937 leukemia cells treated with bufalin at 10(-8) M and above had condensed and fragmented nuclei. Flow cytometric analysis of these cells treated with bufalin showed fragmented DNA smaller than that of the G1 phase. DNA of HL-60 cells treated with bufalin showed a ladder pattern characteristic of apoptosis, as analyzed by agarose gel electrophoretic analysis. DNA synthesis and topoisomerase II activity of HL-60 cells were markedly inhibited as the concentration of bufalin was increased. The concentration needed for inducing apoptosis of HL-60 cells was 10(-8) M, which is comparable to that of camptothecin, but lower than those of other antitumor drugs such as cisplatin, VP16 and all-trans retinoic acid. Apoptosis was not observed when human mononuclear and polymorphonuclear cells were treated with 10(-6) M bufalin for 24 h. These results indicate the association of the growth-inhibitory effect of bufalin with the induction of apoptosis, at least in HL-60 cells, and suggest the usefulness of bufalin for differentiation-apoptosis-inducing therapy for cancer.
Jing
Y
Y
Department of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo.
Ohizumi
H
H
Kawazoe
N
N
Hashimoto
S
S
Masuda
Y
Y
Nakajo
S
S
Yoshida
T
T
Kuroiwa
Y
Y
Nakaya
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002018:Bufanolides / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D004587:Electrophoresis, Agar Gel; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000378:metabolism; D008419:Materia Medica / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009504:Neutrophils / Q000737:chemistry / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002018:Bufanolides; D004273:DNA, Neoplasm; D008419:Materia Medica; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C022777:bufalin