Sak Zafer Hasan Ali, Süzergöz Faruk, Kasumov Veli Tarık, Gürol Ali Osman
Department of Chest Disease, Medical Faculty, Harran University, Sanliurfa, Turkey.
Department of Biology, Science Art Faculty, Harran University, Sanliurfa, Turkey.
Iran J Public Health. 2021 Mar;50(3):550-556. doi: 10.18502/ijph.v50i3.5596.
Non-small cell lung cancer (NSCLC) is responsible for up to 85% of deaths associated with lung cancer. Chemotherapy is still an important treatment method on the treatment of inoperable cases. In this study, the anticancer properties of a series of Schiff bases were tested on the A549 cell line representing NSCLC.
Fluorinated Schiff bases (compounds 1-6) were synthesized based on 2-amino phenylhydrazines and benzaldehydes containing fluorine were used. The cytotoxic effects of the compounds on the A549 cell line were determined by colorimetric MTT assay and the antiproliferative effects of the compounds on the A549 cell line by the CFSE method. To demonstrate the development of apoptosis, cleaved caspase-3 expression in cells was tested using the immunofluorescence method. Morphological changes indicating apoptosis in cells were determined by histopathological staining methods (H & E, giemza, PAP).
The strongest cytotoxic effect on A549 lung cancer cells was obtained with compound 6 (IC50: 0.64 μM) containing 5 fluorine atoms. The strongest antiproliferative effect on A549 cells was achieved with compound 5 (PI: 4.95) carrying 2 fluorine atoms. Apoptosis induction was effective in cell death. In addition to cleaved caspase-3 expression, chromatin condensation, marginalization, and apoptotic bodies were observed in the cells.
Some of the compounds tested showed high cytotoxic and antiproliferative effects, indicating that these compounds could be potential chemotherapeutic agent candidates for lung cancer. The result of immunofluorescence and immunohistochemical analysis showing that the cytotoxic effects have been induced by apoptosis is an important advantage.
非小细胞肺癌（NSCLC）导致了高达85%的肺癌相关死亡。化疗仍然是治疗不可手术病例的重要治疗方法。在本研究中，测试了一系列席夫碱对代表NSCLC的A549细胞系的抗癌特性。
基于2-氨基苯肼合成了含氟席夫碱（化合物1-6），并使用了含氟苯甲醛。通过比色MTT法测定化合物对A549细胞系的细胞毒性作用，通过CFSE法测定化合物对A549细胞系的抗增殖作用。为了证明细胞凋亡的发生，使用免疫荧光法检测细胞中裂解的半胱天冬酶-3的表达。通过组织病理学染色方法（苏木精和伊红染色、吉姆萨染色、过氧化物酶抗过氧化物酶染色）确定细胞中指示凋亡的形态学变化。
含5个氟原子的化合物6（IC50：0.64μM）对A549肺癌细胞具有最强的细胞毒性作用。含2个氟原子的化合物5（PI：4.95）对A549细胞具有最强的抗增殖作用。凋亡诱导在细胞死亡中有效。除了裂解的半胱天冬酶-3表达外，在细胞中还观察到染色质浓缩、边缘化和凋亡小体。
一些测试的化合物显示出高细胞毒性和抗增殖作用，表明这些化合物可能是肺癌潜在的化疗药物候选物。免疫荧光和免疫组织化学分析结果表明细胞毒性作用是由凋亡诱导的，这是一个重要优势。
