Laboratorio de Oncología Experimental, Subdirección de Medicina Experimental, Instituto Nacional de Pediatría, Ciudad de México 04530, Mexico 2 Consorcio de Oncogenómica, Instituto Nacional de Medicina Genómica, Ciudad de México 14610, Mexico.
Consorcio de Oncogenómica, Instituto Nacional de Medicina Genómica, Ciudad de México 14610, Mexico.
Molecules. 2021 Nov 29;26(23):7230. doi: 10.3390/molecules26237230.
Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using crystal violet and trypan blue dyes. Determination of the glutathione (GSH)/glutathione disulfide (GSSG) ratio and levels of carbonylated proteins was performed to evaluate the oxidative stress. Cell cycle progression and induction of cell death by fluorochrome-couple and TUNEL assays were evaluated using flow cytometry assays. Individual treatments with α-mangostin or NDGA decreased the viability of Daoy cells in a dose-dependent manner, inducing G2/M and S-G2/M cell cycle arrest, respectively. Both polyphenols induced cell death and increased oxidative stress. Very interestingly, α-mangostin showed more potent effects than NDGA. Our results indicate that α-mangostin and NDGA exert important cytostatic and cytotoxic effects in the Daoy cell line. These data highlight the potential usefulness of these compounds as an alternative strategy in medulloblastoma treatment.
髓母细胞瘤是儿童期常见的恶性脑肿瘤。目前的治疗方法存在严重的副作用。多酚 α-倒捻子素和去甲二氢愈创木酸（NDGA）在不同的癌症模型中表现出强大的抗肿瘤活性，尽管它们在髓母细胞瘤细胞中的抗肿瘤作用尚未被描述。本研究旨在研究这些多酚对人髓母细胞瘤细胞的促凋亡作用。髓母细胞瘤细胞系 Daoy 用不同浓度的 α-倒捻子素或 NDGA 孵育 24 小时。用结晶紫和台盼蓝染料分析细胞活力。测定谷胱甘肽（GSH）/谷胱甘肽二硫化物（GSSG）比值和羰基化蛋白水平，以评估氧化应激。用荧光染料偶联和 TUNEL 测定法通过流式细胞术评估细胞周期进程和诱导细胞死亡。单独用 α-倒捻子素或 NDGA 处理以剂量依赖的方式降低 Daoy 细胞的活力，分别诱导 G2/M 和 S-G2/M 细胞周期阻滞。两种多酚都诱导细胞死亡和增加氧化应激。非常有趣的是，α-倒捻子素的效果比 NDGA 更显著。我们的结果表明，α-倒捻子素和 NDGA 在 Daoy 细胞系中发挥重要的细胞抑制和细胞毒性作用。这些数据突出了这些化合物作为髓母细胞瘤治疗的替代策略的潜在有用性。
