Allium cepa Linn is commonly used as supplementary folk remedy for cancer therapy. Evidence suggests that Allium extracts have anti-cancer properties. However, the mechanisms of the anti-cancer activity of A. cepa Linn are not fully elucidated in human cancer cells. In this study, we investigated anti-cancer effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in human leukemia cells and their mechanisms. PEAL inhibited cancer cell growth by inducing caspase-dependent apoptosis. The apoptosis was suppressed by caspase 8 and 9 inhibitors. PEAL also up-regulated TNF-related apoptosis-inducing ligand (TRAIL) receptor DR5 and down-regulated survivin and cellular inhibitor of apoptosis 1 (cIAP-1). We confirmed these findings in other leukemic cells (THP-1, K562 cells). In addition, PEAL suppressed Akt activity and the PEAL-induced apoptosis was significantly attenuated in Akt-overexpressing U937 cells. In conclusion, our data suggested that PEAL induced caspase-dependent apoptosis in several human leukemic cells including U937 cells. The apoptosis was triggered through extrinsic pathway by up-regulating DR5 modulating as well as through intrinsic pathway by modulating IAP family members. In addition, PEAL induces caspase-dependent apoptosis at least in part through the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides evidence that PEAL might be useful for the treatment of leukemia.
Keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; 4,6-diamidino-2-phenylindole; Akt; Allium cepa; Apoptosis; DAPI; ELISA; Enzyme-linked immunosorbent assay; FBS; MTT; PBS; PEAL; PI3K; Polyphenols; TNF-related apoptosis-inducing ligand; TRAIL; U937; cIAP; cellular inhibitor of apoptosis; fetal bovine serum; phosphate-buffered saline; phosphatidylinositol 3-kinase; polyphenols extracted from lyophilized Allium cepa Linn.
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