Eid Aya H, Al-Karmalawy Ahmed A, Abdelhameed Reda F A, Mostafa Yasser M, Helal Gouda K, Mehanna Eman T, Hazem Reem M
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, 11785, Egypt.
Department of Pharmaceutical Chemistry, Collage of Pharmacy, The University of Mashreq, Baghdad, 10023, Iraq.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 28. doi: 10.1007/s00210-025-04196-7.
The role of estrogen receptor (ER) and its related effects is crucial for growth of breast cancer cells. This study aimed to assess the cytotoxic impact of alizarin in models of breast cancer in vivo and investigate its antiestrogenic and apoptotic properties. MTT assay was used to evaluate alizarin cytotoxic effect against MCF7 and MDA-MB-231. In vivo, 30 mice were insulted with Ehrlich tumor cells. They were randomly allocated into 3 groups, 10 mice each. Alizarin was orally administered to two treatment groups (50 mg/kg and 100 mg/kg), respectively. The third group was considered as a positive control group. Western blot was used to evaluate the expression of mouse double minute 2 (MDM2), phosphorylated retinoblastoma (pRb), and E2F1. Caspase threefold change was measured by RT-PCR. ERα, Bax, and p53 expressions were investigated by immunohistochemistry. Molecular docking study of alizarin effect on ER was performed. Alizarin demonstrated dose dependent cytotoxicity against MCF7 and MDA-MB cell lines. Alizarin decreased tumor weight in mice, prompted cell cycle arrest, and stimulated cell apoptosis by impeding ERα-mediated tumorigenic effects, and inactivating its related MDM2/p-Rb/E2F1 signaling cascade with upregulation of target genes involved in cell apoptosis (Bax, caspase 3, and p53). Molecular docking proposed that alizarin is a very promising inhibitor to ER. Alizarin represented a promising approach to inhibit cell proliferation of breast cancer by modulating estrogen receptor mediated effects on MDM2/p-Rb/E2F1 axis concomitantly with activating apoptosis of cancer cells.
雌激素受体（ER）的作用及其相关效应对于乳腺癌细胞的生长至关重要。本研究旨在评估茜草素在体内乳腺癌模型中的细胞毒性影响，并研究其抗雌激素和凋亡特性。采用MTT法评估茜草素对MCF7和MDA-MB-231的细胞毒性作用。在体内，用艾氏腹水癌细胞接种30只小鼠。将它们随机分为3组，每组10只小鼠。分别对两个治疗组口服给予茜草素（50mg/kg和100mg/kg）。第三组作为阳性对照组。采用蛋白质免疫印迹法评估小鼠双微体2（MDM2）、磷酸化视网膜母细胞瘤（pRb）和E2F1的表达。通过逆转录聚合酶链反应（RT-PCR）检测半胱天冬酶的三倍变化。通过免疫组织化学研究ERα、Bax和p53的表达。进行了茜草素对ER作用的分子对接研究。茜草素对MCF7和MDA-MB细胞系表现出剂量依赖性细胞毒性。茜草素可降低小鼠肿瘤重量，促使细胞周期停滞，并通过阻碍ERα介导的致瘤作用以及使相关的MDM2/p-Rb/E2F1信号级联失活，同时上调参与细胞凋亡的靶基因（Bax、半胱天冬酶3和p53）来刺激细胞凋亡。分子对接表明茜草素是一种非常有前景的ER抑制剂。茜草素是一种有前景的方法，可通过调节雌激素受体介导的对MDM2/p-Rb/E2F1轴的作用，同时激活癌细胞凋亡来抑制乳腺癌细胞增殖。
