Chipps Elizabeth S, Jayini Renuka, Ando Shoko, Protzman April D, Muhi M Zubayed, Mottaleb M Abdul, Malkawi Ahmed, Islam M Rafiq
Laboratory of Biochemistry, Northwest Missouri State University, 800 University Drive, Maryville, MO 64468, USA.
Nat Prod Commun. 2012 Sep;7(9):1203-8.
Bitter melon (Momordica charantia) seed extracts (BMSE) have been used as traditional medicine for treating various ailments, although in many cases, the active component(s) are unidentified. In this study, bitter melon seeds were extracted in water, ethanol, or ethanol: water (1:1). The aqueous seed extracts (BMSE-W) exhibited marked cytotoxicity towards human embryonic kidney 293T (HEK293T) and human colon tumor 116 (HCT1116) cells. The activity in BMSE-W was unaffected by heat and proteinases treatments, and eluted in the total volume of size-exclusion HPLC, suggesting the small, organic nature of the active component(s). Gas chromatographic-mass spectrometic (GC-MS) analysis of the HPLC fractions identified methoxy-phenyl oxime (MPO) as a major active component. Acetophenone oxime, a commercially available structural homolog of MPO, demonstrated cytotoxicity comparable with that of the BMSE-W. The oxime functional group was found to be critical for activity. Increased poly-(ADP-ribose)-polymerase and beta-actin cleavage, and chromatin condensation observed in treated cells suggested apoptosis as a plausible cause for the cytotoxicity. This study, for the first time, identified a cytotoxic oxime in BMSE-W.
苦瓜（Momordica charantia）种子提取物（BMSE）一直被用作治疗各种疾病的传统药物，尽管在许多情况下，其活性成分尚未明确。在本研究中，苦瓜种子分别用水、乙醇或乙醇：水（1:1）进行提取。水相种子提取物（BMSE-W）对人胚肾293T（HEK293T）细胞和人结肠肿瘤116（HCT1116）细胞表现出显著的细胞毒性。BMSE-W中的活性不受加热和蛋白酶处理的影响，并在尺寸排阻高效液相色谱的总体积中洗脱，这表明活性成分具有小的有机性质。对高效液相色谱馏分进行气相色谱-质谱（GC-MS）分析，确定甲氧基苯肟（MPO）为主要活性成分。苯乙酮肟是一种市售的MPO结构类似物，其细胞毒性与BMSE-W相当。发现肟官能团对活性至关重要。在处理过的细胞中观察到聚（ADP-核糖）聚合酶和β-肌动蛋白的裂解增加以及染色质浓缩，这表明细胞凋亡可能是细胞毒性的原因。本研究首次在BMSE-W中鉴定出一种具有细胞毒性的肟。
