Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, Minia, Egypt.
Anticancer Res. 2021 May;41(5):2383-2395. doi: 10.21873/anticanres.15013.
BACKGROUND/AIM: This study aimed to investigate the effect of the new ciprofloxacin chalcone [7-(4-(N-substituted carbamoyl methyl) piperazin-1 yl)] on the proliferation, migration, and metastasis of MCF-7 and MDA-MB-231 breast cancer cell lines.
Cell viability, colony formation and cell migration abilities were analysed. Cell cycle distribution and apoptosis were examined by flow cytometry. The molecular mechanism underlying chalcone's activity was investigated using qRT-PCR and western blotting.
This new ciprofloxacin chalcone significantly inhibited proliferation, colony formation, and cell migration abilities of both cancer cell lines. Furthermore, it initiated apoptosis and caused cell cycle arrest at G2/M and S phase in MCF-7 and MDA-MB-231 cell lines, respectively. In addition, it up-regulated the expression of pro-apoptotic factors, p53, PUMA and NOXA, and down-regulated the expression of anti-apoptotic factors, MDM2 and MDM4. At the same time, it inhibited epithelial-mesenchymal transition by increasing the expression of E-cadherin and decreasing the expression of TGF-β1, SNAI1, TWIST1, MMP2, and MMP9.
This new ciprofloxacin chalcone exhibited promising apoptotic and anti-metastatic activities against MCF-7 and MDA-MB-231 breast cancer cell lines, and, therefore, is an attractive molecule for drug development in the treatment of breast cancer.
背景/目的：本研究旨在探讨新型环丙沙星查尔酮[7-（4-（N-取代氨甲酰甲基）哌嗪-1-基）]对 MCF-7 和 MDA-MB-231 乳腺癌细胞系增殖、迁移和转移的影响。
分析细胞活力、集落形成和细胞迁移能力。通过流式细胞术检查细胞周期分布和细胞凋亡。使用 qRT-PCR 和 Western blot 研究查尔酮活性的分子机制。
这种新型环丙沙星查尔酮显著抑制了两种癌细胞系的增殖、集落形成和细胞迁移能力。此外，它在 MCF-7 和 MDA-MB-231 细胞系中分别引发凋亡并导致细胞周期在 G2/M 和 S 期停滞。此外，它上调了促凋亡因子 p53、PUMA 和 NOXA 的表达，下调了抗凋亡因子 MDM2 和 MDM4 的表达。同时，它通过增加 E-钙粘蛋白的表达和降低 TGF-β1、SNAI1、TWIST1、MMP2 和 MMP9 的表达来抑制上皮-间充质转化。
这种新型环丙沙星查尔酮对 MCF-7 和 MDA-MB-231 乳腺癌细胞系表现出有希望的凋亡和抗转移活性，因此是治疗乳腺癌药物开发的有吸引力的分子。
