Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.
In Vivo. 2012 Jul-Aug;26(4):657-64.
Comparative study of the growth inhibition by different types of fluoride compounds used in dentistry has been limited. We investigated the effects of sodium fluoride (NaF), diammine silver fluoride [Ag(NH3)2F] and 5-fluorouracil (5-FU) on the growth of eleven human normal and tumor cells in total.
Viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis induction was evaluated by caspase-3 activation and DNA fragmentation. Fluoride was determined using a fluoride-specific electrode.
All compounds had little or no growth stimulating effect (hormesis) on all cells. Ag(NH3)2F exhibited the highest cytotoxicity towards both normal and tumor cells. 5-FU had the selective cytostatic activity towards oral squamous cell carcinoma cell lines, whereas NaF was selectively cytotoxic towards glioblastoma cell lines. None of the compounds induced internucleosomal DNA fragmentation and only 5-FU induced slight activation of caspase-3 in an oral squamous cell carcinoma cell line (HSC-2). Cytotoxicity of fluoride compounds was not reduced by superoxide dismutase and catalase, reducing the possibility of the involvement of reactive oxygen species in the mechanism of action. Approximately 0.01-0.09% initially added NaF was recovered from the cells, whereas the cellular uptake of Ag(NH3)2F and 5-FU was below the detection limit.
Cytotoxicity of fluoride compounds may not be directly linked to their tumor specificity nor to their apoptosis-inducing activity.
用于牙科的不同类型氟化物化合物的生长抑制作用的比较研究一直受到限制。我们研究了氟化钠(NaF)、二氨银氟化物[Ag(NH3)2F]和 5-氟尿嘧啶(5-FU)对 11 个人类正常和肿瘤细胞生长的影响。
通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法测定活细胞数。通过 caspase-3 激活和 DNA 片段化评估细胞凋亡诱导。使用氟化物特异性电极测定氟化物。
所有化合物对所有细胞几乎没有或没有生长刺激作用(适应现象)。Ag(NH3)2F 对正常和肿瘤细胞均表现出最高的细胞毒性。5-FU 对口腔鳞状细胞癌细胞系具有选择性细胞抑制活性,而 NaF 对神经胶质瘤细胞系具有选择性细胞毒性。没有一种化合物诱导核小体间 DNA 片段化,只有 5-FU 在口腔鳞状细胞癌细胞系(HSC-2)中轻微激活 caspase-3。氟化物化合物的细胞毒性不会被超氧化物歧化酶和过氧化氢酶降低,降低了活性氧物质参与作用机制的可能性。从细胞中回收了约 0.01-0.09%最初加入的 NaF,而 Ag(NH3)2F 和 5-FU 的细胞摄取量低于检测限。
氟化物化合物的细胞毒性可能与它们的肿瘤特异性或诱导细胞凋亡的活性无关。