Human oral squamous cell carcinoma (OSCC) poses a significant health challenge in Asia, with current therapeutic strategies failing to improve the survival rates for OSCC patients sufficiently. To elucidate the effects of Nimbolide on OSCC cell proliferation and apoptosis, we performed a series of experiments, including cell proliferation assays, annexin V/PI assays, and cell cycle analysis. We further investigated nimbolide's role in modulating endoplasmic reticulum (ER) stress, reactive oxygen species (ROS) production, and mitochondrial dysfunction using flow cytometry. Additionally, Western blotting was used to detect apoptosis‐related protein expression. Our findings reveal that nimbolide exerts its anti‐proliferative effects on OSCC cells by inducing apoptosis. The nimbolide increased intracellular ROS levels and acceleration of cellular calcium accumulation, respectively promoting endoplasmic reticulum stress and cancer cell apoptosis. Furthermore, nimbolide activates the caspase cascade by altering the mitochondrial membrane potential and apoptotic protein expression, thereby inhibiting the viability of tumor cells. Our data show that Nimbolide suppresses tumor growth through the induction of ROS production, ER stress, and mitochondrial dysfunction, resulting in apoptosis in OSCC cells. Overall, our study highlights nimbolide as a potential natural compound for OSCC therapy.

中文翻译：

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Nimbolide 通过介导人口腔鳞状细胞癌中 ER 应激调节的凋亡信号传导诱导细胞凋亡


人口腔鳞状细胞癌 （OSCC） 在亚洲构成了重大的健康挑战，目前的治疗策略未能充分提高 OSCC 患者的生存率。为了阐明 Nimbolide 对 OSCC 细胞增殖和凋亡的影响，我们进行了一系列实验，包括细胞增殖测定、膜联蛋白 V/PI 测定和细胞周期分析。我们使用流式细胞术进一步研究了 nimbolide 在调节内质网 （ER） 应激、活性氧 （ROS） 产生和线粒体功能障碍中的作用。此外，Western blotting 用于检测细胞凋亡相关蛋白表达。我们的研究结果表明，nimbolide 通过诱导细胞凋亡对 OSCC 细胞发挥抗增殖作用。nimbolide 增加细胞内 ROS 水平并加速细胞钙积累，分别促进内质网应激和癌细胞凋亡。此外，nimbolide 通过改变线粒体膜电位和凋亡蛋白表达来激活 caspase 级联反应，从而抑制肿瘤细胞的活力。我们的数据显示，宁博利通过诱导 ROS 产生、ER 应激和线粒体功能障碍来抑制肿瘤生长，导致 OSCC 细胞凋亡。总体而言，我们的研究强调 nimbolide 是 OSCC 治疗的潜在天然化合物。