髓母细胞瘤（Medulloblastoma，MB）是一组异质性的儿童恶性脑肿瘤，分为具有独特生物特征和预后的分子群。目前可用的治疗方法通常导致患者长期生活质量较差，可能出现神经、神经精神和情绪后遗症。确定能靶向肿瘤而不危害患者生活质量的新型治疗药物至关重要。迷迭香酸（Rosmarinic acid，RA）是一种植物衍生化合物，其对包括癌症在内的一系列疾病的作用已经进行了研究，目前尚未报告任何副作用。以往的研究尚未考察RA在MB中的作用。在这里，我们展示了RA对人Daoy（IC50=168 μM）和D283（IC50=334 μM）MB细胞具有细胞毒性作用。暴露于RA 48小时后，Daoy细胞中组蛋白去乙酰化酶1（Histone deacetylase 1，HDAC1）表达减少，同时增加了H3K9高乙酰化，减少了表皮生长因子（Epidermal growth factor，EGFR）的表达，并抑制了EGFR下游靶点细胞外调节激酶（Extracellular-regulated kinase，ERK）1/2和AKT的激活。这些变化伴随着CDKN1A/p21表达的增加、SOX2表达的减少和增殖速率的下降。RA治疗还降低了癌症干细胞标记物的表达和神经球大小。综上所述，我们的发现表明RA可以减少MB细胞的增殖和干细胞特性，并诱导细胞周期停滞。可能介导这些效应的机制包括靶向HDAC1、EGFR和ERK信号通路，并通过增加H3K9乙酰化和AKT的失活促进p21的表达。RA应进一步研究作为实验性MB的潜在抗癌药物。© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Medulloblastoma (MB) is a heterogeneous group of malignant pediatric brain tumors, divided into molecular groups with distinct biological features and prognoses. Currently available therapy often results in poor long-term quality of life for patients, which will be afflicted by neurological, neuropsychiatric, and emotional sequelae. Identifying novel therapeutic agents capable of targeting the tumors without jeopardizing patients' quality of life is imperative. Rosmarinic acid (RA) is a plant-derived compound whose action against a series of diseases including cancer has been investigated, with no side effects reported so far. Previous studies have not examined whether RA has effects in MB. Here, we show RA is cytotoxic against human Daoy (IC50 = 168 μM) and D283 (IC50 = 334 μM) MB cells. Exposure to RA for 48 h reduced histone deacetylase 1 (HDAC1) expression while increasing H3K9 hyperacetylation, reduced epidermal growth factor (EGFR) expression, and inhibited EGFR downstream targets extracellular-regulated kinase (ERK)1/2 and AKT in Daoy cells. These modifications were accompanied by increased expression of CDKN1A/p21, reduced expression of SOX2, and a decrease in proliferative rate. Treatment with RA also reduced cancer stem cell markers expression and neurosphere size. Taken together, our findings indicate that RA can reduce cell proliferation and stemness and induce cell cycle arrest in MB cells. Mechanisms mediating these effects may include targeting HDAC1, EGFR, and ERK signaling, and promoting p21 expression, possibly through an increase in H3K9ac and AKT deactivation. RA should be further investigated as a potential anticancer agent in experimental MB.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.