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 phytochemical analyses of CMEMM revealed major components included lipids (tetracosanoic acid), sterols (mixture of β-sitosterol and stigmasterol), carbohydrates (sucrose and D-pinitol), triterpenoids (friedelin) and isoflavones (medicarpin, calycosin, afrormosin and genistein). The apoptosis-inducing effects of CMEMM 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 h treatment period. The concentration of CMEMM that exhibited a 50% growth inhibition (IC50) for 72 h exposure was 36.4 μg/ml. Apoptosis triggered by CMEMM in HL-60 cells was confirmed by the following observations: (1) characteristic apoptotic nuclear fragmentation, (2) dose-dependent accumulation of sub-G1 phase in cell cycle analyses, (3) increased percentages of annexin V-positive apoptotic cells, and (4) dose-dependent elevation of active caspase-3. Additionally, the in vivo effect of CMEMM (500 mg/kg/day i.p.) on suppression of HL-60 tumor growth was observed in mouse xenografts. Moreover, CMEMM exerted anti-inflammatory activities by suppressing production of proinflammatory cytokines, TNF-α and IL-6, in lipopolysaccharide-activated RAW264.7 macrophages. These results together suggest that CMEMM exerted a novel antileukemic effects via an apoptotic pathway on HL-60 cells. Further characterization of the active components in CMEMM and their action in antitumor response will be important for future clinical application.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 775.