Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, Taiwan.
Mutat Res. 2012 Sep 18;747(2):253-8. doi: 10.1016/j.mrgentox.2012.06.003. Epub 2012 Jun 18.
Goniothalamin (GTN), a plant bioactive styryl-lactone, is a natural product with potent anti-tumorigenesis effects for several types of cancer. Nonetheless, the anticancer effect of GTN has not been examined in oral cancer. The present study was designed to evaluate its potential anticancer effects in an oral squamous cell carcinoma (OSCC) model and to determine the possible mechanisms with respect to apoptosis, DNA damage, reactive oxygen species (ROS) induction, and mitochondrial membrane potential. Our data demonstrated that cell proliferation was significantly inhibited by GTN in Ca9-22 OSCC cancer cells in concentration- and time-dependent manners (p<0.05). For cell cycle and apoptotic effects of GTN-treated Ca9-22 cancer cells, the sub-G1 population and annexin V-intensity significantly increased in a concentration-dependent manner (p<0.001). For the analysis of DNA double strand breaks, γH2AX intensity significantly increased in GTN-treated Ca9-22 cancer cells in concentration-response relationship (p<0.05). Moreover, GTN significantly induced intracellular ROS levels in Ca9-22 cancer cells in a concentration- and time-dependent manner (p<0.05). For membrane depolarization of mitochondria, the DiOC(2)(3) (3,3'-diethyloxacarbocyanine iodide) intensity of GTN-treated Ca9-22 cancer cells was significantly decreased in concentration- and time-dependent relationships (p<0.001). Taken together, these results suggest that the anticancer effect of GTN against oral cancer cells is valid and GTN-induced growth inhibition and apoptosis influence the downstream cascade including ROS induction, DNA damage, and mitochondria membrane depolarization. Therefore, GTN has potential as a chemotherapeutic agent against oral cancer.
戈尼辛（GTN）是一种植物生物活性的苯乙烯内酯，是一种天然产物，对多种癌症具有很强的抗肿瘤作用。然而，GTN 的抗癌作用尚未在口腔癌中得到检验。本研究旨在评估其在口腔鳞状细胞癌（OSCC）模型中的潜在抗癌作用，并确定与细胞凋亡、DNA 损伤、活性氧（ROS）诱导和线粒体膜电位相关的可能机制。我们的数据表明，GTN 以浓度和时间依赖的方式显著抑制 Ca9-22 口腔鳞状细胞癌细胞的增殖（p<0.05）。对于 GTN 处理的 Ca9-22 癌细胞的细胞周期和凋亡作用，亚 G1 群体和膜联蛋白 V 强度显著增加，呈浓度依赖性（p<0.001）。对于 DNA 双链断裂的分析，GTN 处理的 Ca9-22 癌细胞中 γH2AX 强度呈浓度反应关系显著增加（p<0.05）。此外，GTN 以浓度和时间依赖的方式显著诱导 Ca9-22 癌细胞内的 ROS 水平（p<0.05）。对于线粒体膜去极化，GTN 处理的 Ca9-22 癌细胞的 DiOC（2）（3）（3,3'-二乙氧基羰花青碘化物）强度呈浓度和时间依赖性显著降低（p<0.001）。综上所述，这些结果表明 GTN 对口腔癌细胞的抗癌作用是有效的，GTN 诱导的生长抑制和凋亡影响下游级联反应，包括 ROS 诱导、DNA 损伤和线粒体膜去极化。因此，GTN 具有作为治疗口腔癌的化疗药物的潜力。
