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Abstract：
Background Oral carcinoma presents a significant health challenge, prompting the need for innovative therapeutic approaches. Elevation of inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), has promoted cellular proliferation, inhibited apoptosis, and fostered oral cancer progression through complex signaling pathways. Hesperidin, a flavanone glycoside found in citrus fruits, is of keen interest in this study as it has been proven to have multiple health benefits through in vivo and in vitro studies. However, the mechanism behind the anticancer activity of hesperidin in oral carcinoma remains obscure. Aim The study aimed to explore the anticancer potential of hesperidin on human oral cancer cells (KB cells) by modulating pro-inflammatory and apoptotic signaling mechanisms. Methods Cancer cell growth inhibitory activity was assessed using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Gene expression analysis was performed using real-time RT-PCR analysis. In addition, in silico docking analysis was conducted to confirm the binding affinity of hesperidin with pro-inflammatory and apoptosis signaling molecules. The data were analyzed using one-way ANOVA and the \"t\" test. Results Utilizing the MTT assay, a dose-dependent cytotoxic effect of hesperidin was unveiled, with a remarkable IC50 value indicative of its potent inhibition of cell proliferation. Complementing these findings (p<0.05), qRT-PCR analysis demonstrated hesperidin\'s regulatory influence on key molecular targets within the KB cell line. Hesperidin treatment resulted in a noteworthy reduction in TNF-α, interleukin-1 beta (IL-1-β), IL-6, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and B-cell lymphoma 2 (Bcl-2) mRNA expression levels (p<0.05), highlighting its inhibitory role in cell proliferation, migration, and inflammation processes. Simultaneously, hesperidin promoted the expression of BAX mRNA (p<0.05), indicating an enhancement in cell death. Molecular docking simulations further revealed robust binding affinities between hesperidin and target proteins, suggesting its potential to disrupt cellular functions and inflammatory signaling pathways in oral cancer cells. Conclusion The cytotoxic effects on the KB cell line and its anti-inflammatory properties position hesperidin as a compelling candidate for further exploration in the quest for effective oral carcinoma treatments. These findings shed light on the intricate molecular mechanisms underlying hesperidin\'s promise as a therapeutic agent against oral carcinoma.
摘要：
背景口腔癌提出了重大的健康挑战，促使人们需要创新的治疗方法。炎症介质升高，包括肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6），促进了细胞增殖，抑制细胞凋亡，并通过复杂的信号通路促进口腔癌的进展。橙皮苷,柑橘类水果中发现的黄烷酮苷，在这项研究中非常感兴趣，因为它已被证明具有多种健康益处通过体内和体外研究。然而,橙皮苷在口腔癌中的抗癌活性背后的机制仍然不清楚。目的探讨橙皮苷通过调节促炎和凋亡信号机制对人口腔癌细胞(KB细胞)的抗癌潜力。方法使用MTT（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物）测定法评估癌细胞生长抑制活性。使用实时RT-PCR分析进行基因表达分析。此外,进行了计算机对接分析，以确认橙皮苷与促炎和凋亡信号分子的结合亲和力。使用单因素方差分析和“t”检验分析数据。结果利用MTT测定法，橙皮苷的剂量依赖性细胞毒性作用被揭示，具有显著的IC50值表明其对细胞增殖的有效抑制。补充这些发现(p<0.05)，qRT-PCR分析显示橙皮苷对KB细胞系内关键分子靶标的调控作用。橙皮苷治疗导致TNF-α显著降低，白细胞介素-1β（IL-1-β），IL-6，活化B细胞的核因子κ-轻链增强子（NF-κB），B细胞淋巴瘤2（Bcl-2）mRNA表达水平（p<0.05），强调其在细胞增殖中的抑制作用，迁移,和炎症过程。同时,橙皮苷促进BAXmRNA的表达（p<0.05），表明细胞死亡的增强。分子对接模拟进一步揭示了橙皮苷和靶蛋白之间强大的结合亲和力，提示其可能破坏口腔癌细胞的细胞功能和炎症信号通路。结论橙皮苷对KB细胞系的细胞毒性作用及其抗炎特性使橙皮苷成为寻求有效口腔癌治疗的进一步探索的令人信服的候选者。这些发现揭示了橙皮苷有望作为口腔癌治疗剂的复杂分子机制。
