四氢苯并[h]喹啉对MCF-7人乳腺癌细胞的抗增殖和凋亡作用

Q4 Pharmacology, Toxicology and Pharmaceutics
M. Ghaffari, D. Shanehbandi, Solmaz Sarhadi, Mina Hanifeh Ahagh, Mahsa Maleki Moghaddam, G. Dehghan, R. Ghodsi, Jafar Ezzati Nazhad Dolatabadi
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引用次数: 1

摘要

背景:喹啉及其衍生物在多功能性的基础上显示出多种生物活性,为医药应用设计了一类新的药物。因此,合成新颖多样的喹啉衍生物引起了化学家和生物学家的极大关注。本研究评估了四氢苯并[h]喹啉对密歇根癌症基金会-7 (MCF-7)人乳腺癌细胞的抗增殖和凋亡作用。方法:采用MTT[30 -(4,5 -二甲基噻唑-2-基)- 2,5 -二苯基溴化四唑]法研究四氢苯喹啉的抗增殖作用。通过流式细胞术和末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)对细胞凋亡进行定量和定性研究。采用实时荧光定量PCR (Quantitative real-time PCR, qPCR)和免疫印迹法检测细胞凋亡信号通路相关基因和蛋白的表达水平。结果:合成的化合物在浓度为10µM和7.5µM时,在24和48小时内分别使细胞生长减少50%,并诱导MCF-7癌细胞凋亡达30%。在基因表达水平上,Bcl-2表达明显减轻,Bax表达明显增加。尽管caspase 9的表达显著增加,但处理细胞中caspase 8的表达与对照组相比没有显著差异。Western blotting数据显示Bcl-2、pro-caspase 8、9蛋白表达水平降低。Bax、cleaved-caspase 8、caspase 9蛋白含量显著升高,其中cleaved-caspase 9蛋白含量在处理组显著升高。结论:新合成的四氢苯并[h]喹啉可作为一种很有前途的有机化合物用于治疗癌症,其抗癌作用可通过其他类型的乳腺癌细胞进行研究。体内研究应用于研究该化合物的抗癌效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on MCF-7 human breast cancer cell
Background: Quinoline and its derivatives display various biological activities based on versatility in designing a new drug class for medicinal applications. Hence, synthesizing innovative and varied derivatives of quinoline has gained considerable attention among chemists and biologists. This study evaluated the anti-proliferative and apoptotic effect of tetrahydrobenzo[h]quinoline on Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells. Methods: The anti-proliferative effect of tetrahydrobenzo[h]quinoline was studied via MTT [3 0-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assays. A quantitative and qualitative study of apoptosis was carried out via flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Quantitative real-time PCR (qPCR) and immunoblotting analysis were employed to identify the expression level of genes and proteins involved in the apoptosis signaling pathway. Results: The synthesized compound reduced 50% of cell growth at concentrations of 10 and 7.5 µM during 24 and 48h, respectively, and induced apoptosis up to 30% in MCF-7 cancer cells. Regarding the gene expression level, Bcl-2 displayed considerable alleviation, whereas Bax expression increased significantly. Despite the remarkable increase in caspase 9 expression, there was no noticeable difference in the caspase 8 expression in treated cells compared to the control group. Western blotting data showed that the protein expression level of Bcl-2, pro-caspase 8, and 9 reduced. The protein content of Bax, cleaved-caspase 8, and 9 increased significantly, of which the protein level of cleaved-caspase 9 exhibited a tremendous rise in the treated group. Conclusion: The newly synthesized tetrahydrobenzo[h]quinoline can be a promising organic compound for cancer treatment if its anti-cancer effect investigates by other types of breast cancer cells. In vivo studies should be used to investigate the anti-cancer efficiency of this compound.
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CiteScore
0.10
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17
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