ABSTRACT

The anticancer effects of curcumin are based on the induction of apoptosis, but the specific mechanisms have not yet been fully elucidated. To address this issue, we investigated the effects of curcumin on the intrinsic apoptosis pathway using mitochondria from A549 cells. Curcumin decreased the levels of 14-3-3 proteins, key molecules that inhibit the activation of proapoptotic factors known as BH3-only proteins (e.g. Bad). Curcumin-induced suppression of 14-3-3 protein levels was associated with reduced cytosolic Bad and elevation of mitochondrial Bad, leading to a drop in the mitochondrial membrane potential. 14-3-3 proteins generally interact with Bad phosphorylated by AKT, thus preventing its translocation to the mitochondria where it can promote cell death. Curcumin not only decreased the expression of 14-3-3 proteins but also promoted Bad dephosphorylation in an AKT-dependent fashion. Our results provide novel evidence for the induction of apoptosis by curcumin at multiple stages of the mitochondrial cascade.

摘要

姜黄素的抗癌作用是基于凋亡的诱导，但是具体机制尚未完全阐明。为了解决这个问题，我们研究了姜黄素对使用A549细胞线粒体的内在凋亡途径的影响。姜黄素降低了14-3-3蛋白的水平，这是抑制促凋亡因子活化的关键分子，被称为BH3 Only蛋白（例如Bad）。姜黄素诱导的14-3-3蛋白水平的抑制与胞浆Bad降低和线粒体Bad升高相关，导致线粒体膜电位下降。14-3-3蛋白通常与被AKT磷酸化的Bad相互作用，从而阻止其易位至线粒体，从而促进细胞死亡。姜黄素不仅降低了14-3-3蛋白的表达，而且以AKT依赖的方式促进了Bad去磷酸化。我们的结果为姜黄素在线粒体级联反应的多个阶段诱导凋亡提供了新的证据。