Nasopharyngeal carcinoma (NPC) is an unnoticeable malignant tumor with a high potential of lymphatic metastasis, and its prevalence is high in Asia. Ionizing radiation is the mainstay of treatment for patients with NPC without metastasis. However, patients with metastatic lesions require advanced treatments such as chemotherapy. The present study investigated the apoptotic effect of luteolin-7-O-glucoside on NPC cells and elucidated its underlying signaling mechanisms. The results revealed that luteolin-7-O-glucoside significantly reduced the proliferation of NPC cell lines (NPC-039 and NPC-BM). Flow cytometry and morphological analysis results demonstrated that luteolin-7-O-glucoside treatment induced S and G₂/M cell cycle arrest, chromatin condensation, and apoptosis. In addition, mitochondrial membrane potential was observed to be depolarized with an increasing concentration of luteolin-7-O-glucoside. Proteins involved in the extrinsic and intrinsic pathways of apoptosis, such as death receptor, caspase-3, caspase-8, caspase-9, and Bcl-2 family proteins (Bax, t-Bid, Bcl-2, and Bcl-xL), were downregulated and upregulated after treatment with luteolin-7-O-glucoside, respectively. Moreover, the addition of a PI3K/AKT inhibitor enhanced the activation of poly-ADP-ribose-polymerase (PARP) and attenuated cell viability, indicating that luteolin-7-O-glucoside induced apoptosis in NPC cells through the AKT signaling pathway. These results indicated that the apoptosis of NPC cells modulated by luteolin-7-O-glucoside may be preceded by mitochondrial depolarization, cell cycle arrest, extrinsic and intrinsic apoptosis pathway activation, and AKT signaling modulation. Thus, luteolin-7-O-glucoside can be a promising anticancer agent against human NPC.

中文翻译：

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Luteolin-7-O-glucoside通过AKT信号通路抑制人鼻咽癌细胞增殖并调节细胞凋亡

鼻咽癌（NPC）是一种不易发现的恶性肿瘤，具有很高的淋巴转移潜力，在亚洲地区的患病率很高。电离辐射是无转移的鼻咽癌患者的主要治疗方法。然而，患有转移性病变的患者需要先进的治疗方法，例如化疗。本研究调查了木犀草素 7-O-葡萄糖苷对 NPC 细胞的凋亡作用，并阐明了其潜在的信号传导机制。结果表明，木犀草素-7-O-葡萄糖苷显着降低了 NPC 细胞系（NPC-039 和 NPC-BM）的增殖。流式细胞术和形态学分析结果表明木犀草素-7-O-葡萄糖苷处理诱导S和G ₂/M 细胞周期停滞、染色质凝聚和细胞凋亡。此外，观察到线粒体膜电位随着木犀草素-7-O-葡萄糖苷浓度的增加而去极化。参与细胞凋亡的外在和内在途径的蛋白质，例如死亡受体、caspase-3、caspase-8、caspase-9 和 Bcl-2 家族蛋白（Bax、t-Bid、Bcl-2 和 Bcl-xL） ，分别在用木犀草素-7-O-葡萄糖苷处理后下调和上调。此外，添加 PI3K/AKT 抑制剂增强了多聚 ADP-核糖聚合酶 (PARP) 的活化并减弱了细胞活力，表明木犀草素-7-O-葡萄糖苷通过 AKT 信号通路诱导 NPC 细胞凋亡。这些结果表明，由木犀草素-7-O-葡萄糖苷调节的NPC细胞凋亡可能先于线粒体去极化、细胞周期停滞、外在和内在凋亡通路激活以及AKT信号调节。因此，木犀草素-7-O-葡萄糖苷可能是一种有前途的抗人NPC抗癌剂。