PDF(Pubmed)
Abstract：
Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent.
摘要：
由于出现化学抗性和常规治疗的不良反应，科学界鼓励采用植物衍生化合物来治疗口腔癌。考虑到很少有研究调查丁香酚与牙龈癌的临床相关性，我们应该根据侵略性水平来探索它的选择性和性能。为此,非致癌人口腔上皮细胞（GMSM-K）与舌头（SCC-9）和牙龈（Ca9-22）鳞状细胞癌系一起使用，以评估关键的肿瘤发生过程。总的来说,与正常对应物相比，丁香酚抑制细胞增殖和集落形成，同时诱导癌细胞的细胞毒性。在牙龈癌中记录的作用更大，并且似乎是通过凋亡诱导和p21/p27/cyclinD1调节的促进以及随后在G0/G1期的Ca9-22细胞周期停滞来介导的，以不依赖p53的方式。在这些层面,通过QPCR阵列发现了两种细胞系的不同遗传图谱。此外，似乎我们的活性成分分别通过MMP1/3下调和刺激非活性MMPs复合物形成来限制Ca9-22和SCC-9细胞的迁移。最后,Ca9-22行为似乎主要由P38/STAT5/NFkB途径调节。总之,我们可以发现丁香酚具有癌症选择性，其介导的抗癌机制因细胞系而异，牙龈鳞状细胞癌对这种植物治疗剂更敏感。
