In vitro and in vivo apoptosis-inducing antileukemic effects of Mucuna macrocarpa stem extract on HL-60 human leukemia cells.
Mucuna macrocarpa Wallich (Leguminosae) is believed to hold blood circulation activating effects, and has been used as a folk remedy in Southeast Asia for the treatment of various hematologic and circulatory-related ailments. The objective of this study was to investigate whether crude methanolic extract of M macrocarpa (CMEMM) possessed antileukemic effects on HL-60, human leukemia cells. CMEMM was prepared from dried stems of this plant, and its apoptosis-inducing effects were investigated using HL-60 cells in vitro and in vivo. With treatment of 25 to 75 μg/mL CMEMM, the in vitro antiproliferative effect on HL-60 cells increased in a dose- and time-dependent manner during the 72-hour treatment period. The concentration of CMEMM that exhibited a 50% growth inhibition (IC(50)) for 72-hour exposure was 36.4 μg/mL. Apoptosis triggered by CMEMM in HL-60 cells was confirmed by the following observations: ( a) characteristic apoptotic nuclear fragmentation, (b) dose-dependent accumulation of sub-G(1) phase in cell cycle analyses, (c) increased percentages of annexin V-positive apoptotic cells, and (d) dose-dependent elevation of active caspase-3. Furthermore, an in vivo tumor growth suppression effect by CMEMM (500 mg/kg/d intraperitoneally) was observed in mouse xenografts. The results suggest that CMEMM exerts antileukemic effects via an apoptotic pathway in HL-60 cells, and could be a candidate for developing antileukemic agents in the future.
Lu
Kuan-Hung
KH
China Medical University, No. 91 Hsueh-Shih Road, Taichung, Taiwan.
Chang
Yuh-Fang
YF
Yin
Pen-Hui
PH
Chen
Ting-Ting
TT
Ho
Yu-Ling
YL
Chang
Yuan-Shiun
YS
Chi
Chin-Wen
CW
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D031299:Mucuna; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems
D000972:Antineoplastic Agents, Phytogenic; D028321:Plant Preparations; D053148:Caspase 3