Xanthorrhizol (XNT) is a sesquiterpenoid agent isolated from Curcuma xanthorrhiza; It is known to exhibit various pharmacological activities including anti-cancer. We investigated the anti-cell proliferative and proapoptotic effects of XNT on Non-small cell carcinoma (A549) cells were analyzed by the generation of reactive oxygen species (ROS), alteration of mitochondrial membrane potential (ΔΨm), oxidative DNA damage, and apoptosis morphological changes were explored by Hoechst and AO/EtBr staining. Our study demonstrated that XNT treatment significantly reduced the viability of A549 cells in a concentration-dependent manner. We observed that XNT-induced oxidative stress-mediated apoptotic cell death by increasing intracellular ROS generation, depleting antioxidant levels, enhancing lipid peroxidation, increased apoptotic morphological changes, and % of DNA damage on human lung cancer cells. Furthermore, we observed that the XNT induce apoptosis through inhibits phosphorylation of PI3K, AKTand inhibit NF-κBp65 transcriptional signaling activity. In addition, XNT treatment alters the ΔΨm, thereby induces apoptosis was closely coordinated with the induction of pro-apoptotic markers Bax, Bad, caspase- 3, 9 and cytochrome c, and suppression of anti-apoptotic (Bcl-2, Bcl-XL) protein expression. According to our results, XNT-inducing apoptosis in A549 cells by causing oxidative damage and modulating apoptotic signaling events. Finally, XNT-induced apoptotic cell death was confirmed by the TUNEL assay. Therefore, XNT might be used as a chemotherapeutic agent for the treatment of lung cancer.

中文翻译：

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黄根醇通过调节 PI3K/AKT 和 NF-κB 信号通路抑制非小细胞癌 (A549) 细胞生长并促进细胞凋亡

黄根醇 (XNT) 是一种从姜黄黄根中分离出来的倍半萜类物质；已知显示出包括抗癌在内的各种药理活性。我们研究了 XNT 对非小细胞癌 (A549) 细胞的抗细胞增殖和促凋亡作用，通过活性氧 (ROS) 的产生、线粒体膜电位的改变 ( ΔΨm)、氧化性 DNA 损伤和细胞凋亡形态变化通过 Hoechst 和 AO/EtBr 染色进行探索。我们的研究表明，XNT 处理以浓度依赖性方式显着降低 A549 细胞的活力。我们观察到 XNT 诱导的氧化应激介导的细胞凋亡通过增加细胞内 ROS 的产生、消耗抗氧化剂水平、增强脂质过氧化、增加凋亡形态变化和人肺癌细胞的 DNA 损伤百分比。此外，我们观察到 XNT 通过抑制 PI3K、AKT 的磷酸化并抑制 NF-κBp65 转录信号活性来诱导细胞凋亡。此外，XNT 处理改变了ΔΨm，从而诱导凋亡与促凋亡标志物 Bax、Bad、caspase-3、9 和细胞色素 c 的诱导以及抗凋亡（Bcl-2、Bcl-XL）蛋白表达的抑制密切协调。根据我们的结果，XNT 通过引起氧化损伤和调节凋亡信号事件来诱导 A549 细胞凋亡。最后，通过 TUNEL 测定证实了 XNT 诱导的细胞凋亡。因此，XNT 可能被用作治疗肺癌的化学治疗剂。