Induction of apoptosis in human acute leukemia Jurkat T cells by Albizzia julibrissin extract is mediated via mitochondria-dependent caspase-3 activation.
To understand antitumor activity of Albizzia julibrissin Durazz (Leguminosae), which has been used as a traditional oriental medicine, the mechanism underlying cytotoxic effect of its extract on human acute leukemia Jurkat T cells were investigated. The methanol extract of the stripped barks (3kg) of Albizzia julibrissin was evaporated, dissolved in water, and then sequentially extracted by chloroform, ethyl acetate, and n-butanol. The substance in the butanol extract containing the most cytotoxic activity was further purified by a series of preparative column chromatography. The active substance obtained (723mg) was designated as HaBC18. When Jurkat T cells were treated with HaBC18 (0.5-2microg/ml), apoptosis along with several biochemical events such as mitochondrial cytochrome c release, activation of caspase-9 and -3, degradation of PARP, and DNA fragmentation was induced in a dose-dependent manner. However, the HaBC18-induced apoptosis was abrogated by an ectopic overexpression of Bcl-xL, which is known to block mitochondrial cytochrome c release. Primary cultures of human PBMC were less sensitive to the cytotoxicity relative to Jurkat T cells. These results demonstrate that the cytotoxicity of HaBC18 toward Jurkat T cells is attributable to apoptosis mediated by mitochondria-dependent death-signaling pathway regulated by Bcl-xL.
Won
Hae Jeung
HJ
Department of Life Science and Biotechnology, College of Natural Science, Dongeui University, Busan 614-714, Republic of Korea.
Han
Chang Hee
CH
Kim
Young Ho
YH
Kwon
Hyun Ju
HJ
Kim
Byung Woo
BW
Choi
Jae Soo
JS
Kim
Kwang-Hyeon
KH
D031289:Albizzia; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells / Q000187:drug effects; D007938:Leukemia / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases