背景:口腔癌是全球主要的公共卫生问题,口腔鳞状细胞癌(OSCC)是其最常见的亚型之一。尽管这种疾病的诊断和治疗取得了进展,仍然需要开发新的治疗方法以获得更好的结果.
目的:本研究旨在探讨肉桂酰基磺酰胺异羟肟酸盐衍生物对OSCC的抗癌作用的分子机制。
方法:通过多步过程合成衍生物,然后在分子水平上进行表征。流式细胞术检测DNA含量和细胞周期分布,茴香胺/甲苯胺双染色检测细胞凋亡,以及逆转录聚合酶链反应(RT-PCR)基因表达分析,在暴露于肉桂酰基磺酰胺异羟肟酸盐衍生物的OSCC细胞系上进行。
结果:流式细胞术揭示了用肉桂酰基磺酰胺异羟肟酸盐衍生物处理后,整个OSCC细胞系中细胞分布的显着变化。因此,它导致G0/G1期细胞明显减少,加上S阶段的增加,从而表明在循环的各个点的延迟。此外,在一些化合物处理后,通过茴香胺/甲苯胺双重染色观察到凋亡形态学改变。RT-PCR分析显示p21基因表达水平显著升高,进一步支持化合物诱导细胞周期停滞和细胞凋亡的能力。
结论:该研究强调了肉桂酰基磺酰胺异羟肟酸盐衍生物作为口腔癌候选药物的潜力,特别是OSCC治疗,阐明它们在分子水平上的运作,为开发有助于口腔癌治愈的靶向疗法铺平了道路。
BACKGROUND: Oral cancer is a major public health concern worldwide, with oral squamous cell carcinoma (OSCC) being one of its most common subtypes. Despite advances in diagnosis and management of this disease, there remains a need to develop new therapeutic approaches for better outcomes.
OBJECTIVE: This study aimed to investigate the molecular mechanisms through which cinnamoyl sulfonamide hydroxamate derivatives exert their anticancer effects on OSCC.
METHODS: The derivatives were synthesized via multi-step processes and then characterized at the molecular level. Flow cytometry assay for DNA content and cell cycle distribution, anisidine/
toluidine double staining for apoptosis detection, as well as reverse transcription polymerase chain reaction (RT-PCR) gene expression analysis, were performed on OSCC cell lines exposed to cinnamoyl sulfonamide hydroxamate derivatives.
RESULTS: Flow cytometry unveiled remarkable changes in the distribution of cells throughout the OSCC cell line upon treatment with cinnamoyl sulfonamide hydroxamate derivatives. Consequently, it led to a noticeable decrease in cells at the G0/G1 phase, together with an increase at the S phase, thereby indicating a retardation at various points of the cycle. In addition, apoptotic morphological alterations have been observed by anisidine/
toluidine double staining after some treatments with the compounds. RT-PCR analysis showed a marked increase in p21 gene expression levels, further supporting the compounds\' ability to induce cell cycle arrest and apoptosis.
CONCLUSIONS: The research highlighted the potential of cinnamoyl sulfonamide hydroxamate derivatives as candidates for oral cancer, particularly OSCC treatment, shedding light on their operation at the molecular level and paving the way for the development of targeted therapies that could aid in the cure of oral cancer.