Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells

作者: Joon Hee Park , Cheng-Yun Jin , Bok Kyu Lee , Gi-Young Kim , Yung Hyun Choi

DOI: 10.1016/J.FCT.2008.09.056

关键词:

摘要: Naringenin (NGEN), one of the most abundant flavonoids in citrus fruits, has been shown to inhibit vitro growth human cancer cells, although mechanism action is poorly understood. Herein, we investigated NEGN's pro-apoptotic effect on leukemia THP-1 cells. NGEN treatment inhibited cells' a concentration-dependent manner by inducing apoptosis, as evidenced formation apoptotic bodies and accumulation cells sub-G1 phase. NGEN-induced apoptosis was accompanied increased hyperpolarization mitochondrial membrane potential, downregulation Bcl-2, upregulation Bax, activation caspases subsequent poly(ADP-ribose)polymerase (PARP) cleavages. z-DEVD-fmk, caspase-3 inhibitor, significantly both cytotoxic characteristics induced demonstrating caspase-3's important role observed effect. The induction also associated with inactivation phosphatidylinositol 3-kinase (PI3K)/Akt, PI3K inhibitor LY29004 increases cell death. These findings provide evidence that mediated mitochondria dysfunctions correlate PI3K/Akt pathway Therefore, strong potential therapeutic agent for preventing cancers such leukemia.

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