Yuan Bo, Kikuchi Hidetomo
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado 350-0295, Saitama, Japan.
Laboratory of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado 350-0295, Saitama, Japan.
Cells. 2024 Dec 23;13(24):2138. doi: 10.3390/cells13242138.
Glioblastoma (GBM) is the most common and lethal intracranial tumor in adults. Despite advances in the understanding of the molecular events responsible for disease development and progression, survival rates and mortality statistics for GBM patients have been virtually unchanged for decades and chemotherapeutic drugs used to treat GBM are limited. Arsenic derivatives, known as highly effective anticancer agents for leukemia therapy, has been demonstrated to exhibit cytocidal effects toward GBM cells by inducing cell death, cell cycle arrest, inhibition of migration/invasion, and angiogenesis. Differentiation induction of glioma stem-like cells (GSCs) and inhibition of neurosphere formation have also been attributed to the cytotoxicity of arsenic derivatives. Intriguingly, similar cytotoxic effects against GBM cells and GSCs have also been observed in natural agents such as anthocyanidins, tetrandrine, and bufadienolides. In the current review, we highlight the available data on the molecular mechanisms underlying the multifaceted anticancer activity of arsenic compounds and natural agents against cancer cells, especially focusing on GBM cells and GCSs. We also outline possible strategies for developing anticancer therapy by combining natural agents and arsenic compounds, as well as temozolomide, an alkylating agent used to treat GBM, in terms of improvement of chemotherapy sensitivity and minimization of side effects.
胶质母细胞瘤（GBM）是成人中最常见且致命的颅内肿瘤。尽管在理解导致疾病发生和进展的分子事件方面取得了进展，但GBM患者的生存率和死亡率统计数据几十年来几乎没有变化，用于治疗GBM的化疗药物也很有限。砷衍生物作为治疗白血病的高效抗癌剂，已被证明可通过诱导细胞死亡、细胞周期停滞、抑制迁移/侵袭和血管生成，对GBM细胞产生杀细胞作用。胶质瘤干细胞样细胞（GSCs）的分化诱导和神经球形成的抑制也归因于砷衍生物的细胞毒性。有趣的是，在花青素、粉防己碱和蟾蜍二烯羟酸内酯等天然药物中也观察到了对GBM细胞和GSCs类似的细胞毒性作用。在本综述中，我们重点介绍了关于砷化合物和天然药物对癌细胞多方面抗癌活性的分子机制的现有数据，尤其关注GBM细胞和GCSs。我们还概述了通过将天然药物与砷化合物以及替莫唑胺（一种用于治疗GBM的烷基化剂）联合使用来开发抗癌疗法的可能策略，以提高化疗敏感性并将副作用降至最低。
