胶质母细胞瘤 (GBM) 是一种侵袭性癌症，每年影响数千人的中枢神经系统 (CNS)。氧化还原改变已被证明在这些肿瘤的发生和进展中发挥着关键作用，因为活性氧 (ROS) 的形成涉及多种信号传导途径、转录因子和细胞因子形成的调节。第二代口服烷化剂替莫唑胺（TMZ）是治疗GBM的一线化疗药物，但患者常出现原发性和继发性耐药，降低其疗效。抗氧化剂是有前途和潜在的辅助剂，因为它们可以减少化疗和放疗产生的过量ROS形成，同时降低药理学耐药性。 S-烯丙基半胱氨酸 (SAC) 已被证明可以抑制多种类型癌细胞的增殖，但其精确的抗增殖机制仍缺乏研究。迄今为止，SAC 效应在 GBM 细胞中的研究还很少。在这里，我们在体外研究了 SAC 单独或与 TMZ 联合使用，对来自大鼠的两种胶质母细胞瘤细胞系 RG2 和 C6 中的几个毒性和调节终点（包括氧化应激标记物和转录调节）的影响，以阐明一些其抗增殖特性的生化和细胞机制。 SAC (1-750 µM) 以浓度依赖性方式降低两种细胞系的细胞活力，尽管 C6 细胞在几个测试浓度下对 SAC 更具抵抗力。 TMZ 还产生浓度依赖性效应，降低两种细胞系的细胞活力。结合起来，SAC（1 µM 或 100 µM）和 TMZ（500 µM）可以增强彼此的效果。 SAC 还增强了 TMZ 的脂质过氧化作用，并通过减少 TMZ 诱导的 GSH/GSSG 比率增加来降低两种细胞系的细胞抗氧化性。在RG2和C6细胞中，SAC本身对Nrf2/ARE结合活性没有影响，而在RG2细胞中，TMZ和SAC  TMZ的组合降低了这种活性。我们的结果表明，SAC 单独或与 TMZ 联合使用，可通过氧化还原活性反应的调节机制介导发挥抗肿瘤作用。 SAC 也是一种用于其他模型测试的安全药物，因为它在原代星形胶质细胞中产生无毒作用。综合起来，这些作用表明 SAC 具有抗氧化特性和潜在的抗 GBM 抗肿瘤功效。© 2024。作者。

Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints-including oxidative stress markers and transcriptional regulation-in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1-750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM.© 2024. The Author(s).