Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Molecules. 2023 Jan 23;28(3):1137. doi: 10.3390/molecules28031137.
Novel drugs are desperately needed in order to combat a significant challenge due to chemo-therapeutic resistance and bad prognosis. This research aimed to assess the anticancer activity of a newly synthesized ciprofloxacin Mannich base (CMB) on ovarian cancer (OVCAR-3) and lung cancer (A-549) cell lines and to investigate probable involved molecular mechanisms. The cytotoxic and pro-apoptotic impact of CMB on both cell lines was investigated using MTT assay, Annexin V assay, and cell cycle analysis, as well as caspase-3 activation. Western blotting was carried out to evaluate downstream targets of the MAPK pathway, while qRT PCR was used to evaluate the gene expression pattern of the p53/Bax/Bcl2 pathway. CMB treatment showed significantly reduced cell proliferation in both OVCAR-3 and A-549 cells with half maximum inhibitory concentration (IC) = 11.60 and 16.22 µg/mL, respectively. CMB also induced apoptosis, S phase cell cycle arrest, and up-regulated expression of p53, p21, and Bax while down-regulated Bcl2 expression. CMB also halted cell proliferation by deactivating the MAPK pathway. In conclusion, CMB may be regarded as a potential antiproliferative agent for lung and ovarian cancers due to anti-proliferative and pro-apoptotic actions via inhibition of the MAPK pathway and p53/Bax/Bcl2.
为了应对化疗耐药和预后不良这一重大挑战，我们急需新型药物。本研究旨在评估新型合成环丙沙星曼尼希碱（CMB）对卵巢癌（OVCAR-3）和肺癌（A-549）细胞系的抗癌活性，并探讨其可能的涉及的分子机制。我们通过 MTT 检测、Annexin V 检测、细胞周期分析和 caspase-3 激活实验，研究了 CMB 对这两种细胞系的细胞毒性和促凋亡作用。我们还通过 Western blot 评估了 MAPK 通路的下游靶标，通过 qRT-PCR 评估了 p53/Bax/Bcl2 通路的基因表达模式。CMB 处理显著降低了 OVCAR-3 和 A-549 细胞的增殖，其半最大抑制浓度（IC）分别为 11.60 和 16.22μg/ml。CMB 还诱导了细胞凋亡、S 期细胞周期阻滞，并上调了 p53、p21 和 Bax 的表达，同时下调了 Bcl2 的表达。CMB 还通过抑制 MAPK 通路来阻止细胞增殖。总之，CMB 可能被视为一种潜在的抗肺癌和卵巢癌的增殖剂，因为它通过抑制 MAPK 通路和 p53/Bax/Bcl2 发挥抗增殖和促凋亡作用。
