Department of Natural Sciences, Lebanese American University, Beirut 13-5053, Lebanon.
Laboratory of Regenerative Hematopoiesis, Swiss Institute for Experimental Cancer Research (ISREC) & Institute of Bioengineering (IBI), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Toxins (Basel). 2019 Aug 30;11(9):506. doi: 10.3390/toxins11090506.
Mill is a large green fruit with black seeds widely known to possess toxic properties due to the presence of Annonaceous acetogenins. The present study investigates the anti-cancer properties of an Mill ethanolic seed extract on Acute Myeloid Leukemia (AML) cell lines in vitro and elucidates the underlying cellular mechanism. The anti-proliferative effects of the extract on various AML cell lines and normal mesenchymal cells (MSCs) were assessed using WST-1 viability reagent. The pro-apoptotic effect of the extract was evaluated using Annexin V/PI staining and Cell Death ELISA. The underlying mechanism was deciphered by analyzing the expression of various proteins using western blots. Treatment with an seed ethanolic extract promotes a dose- and time-dependent inhibition of the proliferation of various AML cell lines, but not MSCs. Positive Annexin V staining, as well as DNA fragmentation, confirm an increase in apoptotic cell death by upregulating the expression of pro-apoptotic proteins which control both intrinsic and extrinsic pathways of apoptosis. GC/MS analysis revealed the presence of phytosterols, in addition to other bioactive compounds. In conclusion, Mill seed extract, previously known to possess a potent toxic activity, induces apoptosis in AML cell lines by the activation of both the extrinsic and the intrinsic pathways.
腰果是一种大型绿色水果，其黑色种子广为人知，由于含有番荔枝乙酰酯酶，具有毒性。本研究探讨了腰果乙醇种子提取物对体外急性髓系白血病（AML）细胞系的抗癌特性，并阐明了潜在的细胞机制。使用 WST-1 活力试剂评估提取物对各种 AML 细胞系和正常间充质细胞（MSCs）的抗增殖作用。通过 Annexin V/PI 染色和细胞死亡 ELISA 评估提取物的促凋亡作用。通过使用蛋白质印迹分析来解析各种蛋白质的表达来破译潜在的机制。用 种子乙醇提取物处理可促进各种 AML 细胞系的增殖受到剂量和时间依赖性抑制，但对 MSCs 没有影响。阳性 Annexin V 染色以及 DNA 片段化证实通过上调控制细胞凋亡内在和外在途径的促凋亡蛋白的表达，凋亡细胞死亡增加。GC/MS 分析表明除了其他生物活性化合物外，还存在植物甾醇。总之，先前已知具有强烈毒性活性的腰果种子提取物通过激活外在和内在途径诱导 AML 细胞系凋亡。
