Cherian Eapen, Goyal Manoj, Mittal Neeti, Yesodharan Venu, Ramadoss Ramya, Thomas Cinu
Oral Pathology and Oral Biology, Travancore Dental College, Kollam, IND.
Oral & Maxillofacial Surgery, Santosh Deemed to be University, Ghaziabad, IND.
Cureus. 2023 Aug 22;15(8):e43949. doi: 10.7759/cureus.43949. eCollection 2023 Aug.
Background Cancer is the second most common cause of death. Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms. Many treatment modalities such as chemotherapy, radiotherapy, surgery, and immunotherapy are emerging but still, the patients' quality of life is questionable. Despite the advances in therapeutic approaches, the percentages of morbidity and mortality of OSCC have not improved significantly during the last 30 years. Treatment using natural products can act as a potent anti-cancer agent with reduced adverse effects. Cinnamic acid derivatives exhibit anti-cancer potential through histone deacetylase inhibitor (HDAC) enzyme inhibition. Methodology In an experimental study design, cinnamoyl hydroxamate derivatives were prepared. The structure was confirmed using ultraviolet-visible spectroscopy (UV-Vis), nuclear magnetic resonance (NMR), infrared spectroscopy, and mass spectrophotometry. An in-vitro antioxidant assay using nitric oxide scavenging and reducing power assay was done and an in-vitro cytotoxic (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay and viability assay were carried out using tryphan blue dye. Results Statistical analysis was performed using SPSS (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp). Cinnamoyl hydroxamate derivatives were obtained and named as compounds 3a (E)-N-Hydroxy-3-(4-(N-(phenyl bromo) sulfamoyl) phenyl) acrylamide-) and 3b ((E)-N-Hydroxy-3-(4-(N-(phenyl nitro) sulfamoyl) phenyl) acrylamide). In the nitric oxide scavenging assay, compound 3a showed good antioxidant activity than 3b. Reducing power assay was higher in 3a compared to 3b. Cell viability using tryphan blue exhibited a concentration decrease in % cell viability with an increase in the concentration of human oral cavity squamous cell carcinoma cell line (OECM 1), a unique head and neck squamous carcinoma cell line (UM SCC 6) & human oral squamous cell carcinoma forming metastatic foci (HSC 3) cell lines. Conclusion The results of the present study revealed that the study compounds play a vital role in the up-regulation of apoptotic pathways and regulation of terminal differentiation pathways. The compounds showed good anti-oxidant and anti-cancer activities in lesser concentrations, hence they can be used as a therapeutic agent for oral squamous cell carcinoma.
背景 癌症是第二大常见死因。口腔鳞状细胞癌（OSCC）是所有口腔肿瘤中最常见的。许多治疗方式如化疗、放疗、手术和免疫疗法不断涌现，但患者的生活质量仍存在问题。尽管治疗方法有所进步，但在过去30年里，OSCC的发病率和死亡率并未显著改善。使用天然产物进行治疗可作为一种有效的抗癌剂，且副作用较小。肉桂酸衍生物通过抑制组蛋白脱乙酰酶（HDAC）发挥抗癌潜力。
方法 在一项实验研究设计中，制备了肉桂酰异羟肟酸酯衍生物。使用紫外可见光谱（UV-Vis）、核磁共振（NMR）、红外光谱和质谱对其结构进行了确认。进行了一氧化氮清除和还原能力测定的体外抗氧化试验，并使用台盼蓝染料进行了体外细胞毒性（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐）（MTT）试验和活力试验。
结果 使用SPSS（IBM公司。2013年发布。适用于Windows的IBM SPSS Statistics，版本22.0。纽约州阿蒙克：IBM公司）进行统计分析。获得了肉桂酰异羟肟酸酯衍生物，并将其命名为化合物3a（（E）-N-羟基-3-（4-（N-（苯基溴）磺酰基）苯基）丙烯酰胺）和3b（（E）-N-羟基-3-（4-（N-（苯基硝基）磺酰基）苯基）丙烯酰胺）。在一氧化氮清除试验中，化合物3a的抗氧化活性优于3b。3a的还原能力测定结果高于3b。使用台盼蓝测定细胞活力显示，随着人口腔鳞状细胞癌细胞系（OECM 1）、一种独特的头颈鳞状癌细胞系（UM SCC 6）和形成转移灶的人口腔鳞状细胞癌（HSC 3）细胞系浓度的增加，细胞活力百分比降低。
结论 本研究结果表明，所研究的化合物在凋亡途径的上调和终末分化途径的调节中起着至关重要的作用。这些化合物在较低浓度下显示出良好的抗氧化和抗癌活性，因此可作为口腔鳞状细胞癌的治疗药物。
