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Abstract：
Oral cancer is the eleventh most prevalent cancer worldwide. The most prevalent oral cancer is oral squamous cell carcinoma (OSCC). Damnacanthal (DAM) and nordamnacanthal (NDAM), the anthraquinone compounds, are isolated from the root of Morinda citrifolia L. (Noni), which has been used for the treatment of several chronic diseases including cancer. The objectives of this study were to evaluate the cytotoxicity, cell death mode, cell cycle, and the molecular mechanism of apoptosis induced by DAM and NDAM on OSCC. The cytotoxic effects of these compounds against OSCC cell lines were determined by MTT assay. The cell death mode was analysed by DNA laddering and FITC-annexin V/PI flow cytometric assays. In addition, the mechanism of apoptosis induced by DAM and NDAM was detected using mitochondrial membrane potential, Cytochrome c, and caspases assays. Finally, the effect of DAM and NDAM on cell cycle phase distribution of OSCC cells was detected by flow cytometry. In the present study, DAM and NDAM showed cytotoxicity towards OSCC cell lines and the maximum growth inhibition for both compounds was observed in H400 cells with IC50 value of 1.9 and 6.8 μg/ml, respectively, after 72 h treatment. The results also demonstrated the inhibition of H400 OSCC cells proliferation, internucleosomal cleavage of DNA, activation of intrinsic apoptosis pathway, and cell cycle arrest caused by DAM and NDAM. Therefore, these findings suggest that DAM and NDAM can be potentially used as antitumor agents for oral cancer therapy.
摘要：
口腔癌是全球第11位最普遍的癌症。最普遍的口腔癌是口腔鳞状细胞癌(OSCC)。Damnacanthal（DAM）和nordamnacanthal（NDAM），蒽醌化合物，从巴林达根中分离出来（诺丽），已用于治疗包括癌症在内的多种慢性疾病。本研究的目的是评估细胞毒性，细胞死亡模式，细胞周期,以及DAM和NDAM诱导OSCC细胞凋亡的分子机制。通过MTT测定确定这些化合物对OSCC细胞系的细胞毒性作用。通过DNA梯级法和FITC-膜联蛋白V/PI流式细胞术分析细胞死亡模式。此外,用线粒体膜电位检测DAM和NDAM诱导细胞凋亡的机制,细胞色素c,和胱天蛋白酶测定。最后,流式细胞术检测DAM和NDAM对OSCC细胞细胞周期时相分布的影响。在本研究中,DAM和NDAM显示对OSCC细胞系的细胞毒性，并且在H400细胞中观察到两种化合物的最大生长抑制，IC50值为1.9和6.8μg/ml。分别,治疗72小时后。结果还证明了H400对OSCC细胞增殖的抑制作用，DNA的核小体间裂解，内在凋亡途径的激活，以及DAM和NDAM引起的细胞周期停滞。因此,这些发现提示DAM和NDAM有可能作为抗肿瘤药物用于口腔癌治疗.
