The Anti-Tumor Effect of Flaxseed Lignan Derivatives on Different Acute Myeloid Leukemia Cancer Cells

Abstract

Flaxseeds have recently become a main food on the “superfoods” list. They contain many different compounds that make them beneficial for human health. The most abundant plant lignan ingested through flax, secoisolariciresinol diglucoside (SDG), is metabolically converted into two mammalian lignan derivatives, namely Enterodiol (END) and Enterolactone (ENL). Some studies have reported the anti-cancerous effect of these flaxseed derivatives in mice for some cancer types. In this study, we investigated the effect of SDG, END and ENL on the proliferation of acute myeloid leukemia cells (AML) in vitro. Cytotoxicity assays, using WST-1, revealed dose- and time- dependent effects in various AML cell lines with the most prominent cytotoxicity exhibited by ENL. Interestingly, no effects were detected in normal cells affirming the selectivity of ENL in promoting death of leukemic cells only. Annexin V staining confirmed the abundance of phosphatidylserine on the outer membrane leaflet in KG1 cells treated with ENL, indicating the activation of apoptotis. Moreover, Cell Death ELISA analysis showed a dose-dependent increase in apoptosis, as revealed by an increase in DNA fragmentation. Pro-apoptotic proteins expression was assessed using Western blot analysis which further confirmed the activation of apoptotic mechanisms upon ENL exposure. In conclusion, ENL which was revealed to be the most cytotoxic lignan against AML cells, trigger cell death via the intrinsic apoptotic pathway. Subsequent investigations need to be performed to confirm the anti-tumor effect of ENL in vivo.