Programa de Pós-Graduação em Farmacologia e Bioquímica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil.
Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-110, Brazil.
Molecules. 2022 Dec 13;27(24):8850. doi: 10.3390/molecules27248850.
Gliomas are the most common primary malignant brain tumors in adults, and have a poor prognosis, despite the different types of treatment available. There is growing demand for new therapies to treat this life-threatening tumor. Quinone derivatives from plants have received increased interest as potential anti-glioma drugs, due to their diverse pharmacologic activities, such as inhibiting cell growth, inflammation, tumor invasion, and promoting tumor regression. Previous studies have demonstrated the anti-glioma activity of , which is related to three main naphthoquinone compounds-eleutherine, isoeleutherine, and eleutherol-but their mechanism of action remains elusive. Thus, the aim of this study was to investigate the mechanism of action of eleutherine on rat C6 glioma. In vitro cytotoxicity was evaluated by MTT assay; morphological changes were evaluated by phase-contrast microscopy. Apoptosis was determined by annexin V-FITC-propidium iodide staining, and antiproliferative effects were assessed by wound migration and colony formation assays. Protein kinase B (AKT/pAKT) expression was measured by western blot, and telomerase reverse transcriptase mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Eleutherine reduced C6 cell proliferation in a dose-dependent manner, suppressed migration and invasion, induced apoptosis, and reduced AKT phosphorylation and telomerase expression. In summary, our results suggest that eleutherine has potential clinical use in treating glioma.
神经胶质瘤是成人中最常见的原发性恶性脑肿瘤，尽管有不同类型的治疗方法，但预后仍较差。由于其多种药理活性，如抑制细胞生长、炎症、肿瘤侵袭和促进肿瘤消退，植物醌衍生物作为潜在的抗神经胶质瘤药物越来越受到关注。先前的研究已经证明了 ，这与三种主要的萘醌化合物——刺桐碱、异刺桐碱和刺桐醇有关，但它们的作用机制仍不清楚。因此，本研究旨在探讨刺桐碱对大鼠 C6 神经胶质瘤的作用机制。通过 MTT 测定法评估体外细胞毒性；相差显微镜评估形态变化。通过 Annexin V-FITC-碘化丙啶染色测定细胞凋亡，通过划痕迁移和集落形成测定评估抗增殖作用。通过 Western blot 测定蛋白激酶 B (AKT/pAKT) 的表达，并通过实时定量聚合酶链反应 (qRT-PCR) 测定端粒酶逆转录酶 mRNA 的表达。刺桐碱呈剂量依赖性降低 C6 细胞增殖，抑制迁移和侵袭，诱导细胞凋亡，并降低 AKT 磷酸化和端粒酶表达。综上所述，我们的研究结果表明，刺桐碱在治疗神经胶质瘤方面具有潜在的临床应用价值。
