Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av, Prof, Lineu Prestes, 1524, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
J Exp Clin Cancer Res. 2013 May 23;32(1):31. doi: 10.1186/1756-9966-32-31.
Anticancer activities of cinnamic acid derivatives include induction of apoptosis by irreversible DNA damage leading to cell death. The present work aimed to compare the cytotoxic and genotoxic potential of cinnamic acid in human melanoma cell line (HT-144) and human melanocyte cell line derived from blue nevus (NGM). Viability assay showed that the IC50 for HT-144 cells was 2.4 mM, while NGM cells were more resistant to the treatment. The growth inhibition was probably associated with DNA damage leading to DNA synthesis inhibition, as shown by BrdU incorporation assay, induction of nuclear aberrations and then apoptosis. The frequency of cell death caused by cinnamic acid was higher in HT-144 cells. Activated-caspase 3 staining showed apoptosis after 24 hours of treatment with cinnamic acid 3.2 mM in HT-144 cells, but not in NGM. We observed microtubules disorganization after cinnamic acid exposure, but this event and cell death seem to be independent according to M30 and tubulin labeling. The frequency of micronucleated HT-144 cells was higher after treatment with cinnamic acid (0.4 and 3.2 mM) when compared to the controls. Cinnamic acid 3.2 mM also increased the frequency of micronucleated NGM cells indicating genotoxic activity of the compound, but the effects were milder. Binucleation and multinucleation counting showed similar results. We conclude that cinnamic acid has effective antiproliferative activity against melanoma cells. However, the increased frequency of micronucleation in NGM cells warrants the possibility of genotoxicity and needs further investigation.
肉桂酸衍生物的抗癌活性包括通过导致细胞死亡的不可逆 DNA 损伤诱导细胞凋亡。本工作旨在比较肉桂酸对人黑色素瘤细胞系(HT-144)和源自蓝痣的人黑素细胞系(NGM)的细胞毒性和遗传毒性潜力。细胞活力测定表明,HT-144 细胞的 IC50 为 2.4 mM,而 NGM 细胞对该处理的抵抗力更强。生长抑制可能与导致 DNA 合成抑制的 DNA 损伤有关,如 BrdU 掺入测定、核畸变诱导和随后的细胞凋亡所显示的。肉桂酸引起的细胞死亡频率在 HT-144 细胞中更高。肉桂酸 3.2 mM 处理 24 小时后,HT-144 细胞中激活的 caspase 3 染色显示细胞凋亡,但在 NGM 细胞中未观察到。在用肉桂酸处理后,我们观察到微管解聚,但根据 M30 和微管蛋白标记,这种事件和细胞死亡似乎是独立的。与对照相比,肉桂酸(0.4 和 3.2 mM)处理后 HT-144 细胞中的微核细胞频率更高。肉桂酸 3.2 mM 还增加了微核化 NGM 细胞的频率,表明该化合物具有遗传毒性活性,但作用较为温和。双核和多核计数显示出相似的结果。我们得出结论,肉桂酸对黑色素瘤细胞具有有效的抗增殖活性。然而,NGM 细胞中微核形成频率的增加表明存在遗传毒性的可能性,需要进一步研究。