Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2020-10-17 , DOI: 10.1016/j.biopha.2020.110884 Stephanie Tannous , Tony Haykal , Jana Dhaini , Mohammad Hassan Hodroj , Sandra Rizk
Flaxseeds have been known for their anti-cancerous effects due to the high abundance of lignans released upon ingestion. The most abundant lignan, secoisolariciresinol diglucoside (SDG), is ingested during the dietary intake of flax, and is then metabolized in the gut into two mammalian lignan derivatives, Enterodiol (END) and Enterolactone (ENL). These lignans were previously reported to possess anti-tumor effects against breast, colon, and lung cancer.
This study aims to investigate the potential anti-cancerous effect of the flaxseed lignans SDG, END and ENL on acute myeloid leukemia cells (AML) in vitro and to decipher the underlying molecular mechanism. AML cell lines, (KG-1 and Monomac-1) and a normal lymphoblastic cell line were cultured and treated with the purified lignans. ENL was found to be the most promising lignan, as it exhibits a significant selective dose- and time-dependent cytotoxic effect in both AML cell lines, contrary to normal cells. The cytotoxic effects observed were attributed to apoptosis induction, as revealed by an increase in Annexin V staining of AML cells with increasing ENL concentrations. The increase in the percentage of cells in the pre-G phase, in addition to cell death ELISA analysis, validated cellular and DNA fragmentation respectively. Analysis of protein expression using western blots confirmed the activation of the intrinsic apoptotic pathway upon ENL treatment. This was also accompanied by an increase in ROS production intracellularly. In conclusion, this study demonstrates that ENL has promising anti-cancer effects in AML cell lines in vitro, by promoting DNA fragmentation and the intrinsic apoptotic pathway, highlighting the protective health benefits of flax seeds in leukemia.
中文翻译:
亚麻籽木脂素衍生物对不同急性髓系白血病癌细胞的抗癌作用
亚麻籽因其抗癌作用而闻名,这是由于摄入后释放出大量木酚素所致。饮食中摄入亚麻中最丰富的木脂素,异豆香脂树脂二葡萄糖苷(SDG),然后在肠道中代谢成两种哺乳动物的木脂素衍生物,肠二醇(END)和肠内酯(ENL)。以前有报道称这些木脂素对乳腺癌,结肠癌和肺癌具有抗肿瘤作用。
本研究旨在调查亚麻籽的潜在的抗癌症作用的木酚素SDG,对急性髓系白血病细胞(AML)END和ENL在体外并解释潜在的分子机制。培养AML细胞系(KG-1和Monomac-1)和正常淋巴细胞细胞系,并用纯化的木脂素处理。发现ENL是最有前途的木脂素,因为与正常细胞相反,它在两种AML细胞系中均表现出显着的选择性剂量依赖性和时间依赖性细胞毒性作用。观察到的细胞毒性作用归因于细胞凋亡的诱导,这通过AML细胞的膜联蛋白V染色随ENL浓度的增加而增加。除细胞死亡ELISA分析外,pre-G期细胞百分比的增加分别验证了细胞和DNA片段化。使用蛋白质印迹的蛋白质表达分析证实了ENL处理后固有的凋亡途径的激活。这还伴随着细胞内ROS产生的增加。总之,这项研究表明ENL在AML细胞系中具有有希望的抗癌作用在体外,通过促进DNA片段化和固有的凋亡途径,突出了亚麻籽对白血病的保护健康益处。