PDF(Pubmed)
Abstract：
Glioblastoma (GBM) is one of the most aggressive cancers, characterized by a decrease in antioxidant levels. Evidence has demonstrated that ferulic acid (FA), a natural antioxidant particularly abundant in vegetables and fruits, could be a promising candidate for GBM treatment. Since FA shows a high instability that compromises its therapeutic application, it has been encapsulated into Nanostructured Lipid Carriers (NLCs) to improve its bioavailability in the brain. It has been demonstrated that tissue transglutaminase (TG2) is a multi-functional protein implicated in many physiological and pathological processes, including cancer. TG2 is also involved in GBM correlated with metastasis formation and drug resistance. Therefore, the evaluation of TG2 expression levels and its cellular localization are important to assess the anti-cancer effect of FA against GBM cancer. Our results have demonstrated that treatment with free FA and FA-NLCs in the U87-MG cancer cell line differently modified TG2 localization and expression levels. In the cells treated with free FA, TG2 appeared expressed both in the cytosol and in the nucleus, while the treatment with FA-NLCs showed that the protein is exclusively localized in the cytosol, exerting its pro-apoptotic effect. Therefore, our data suggest that FA loaded in NLCs could represent a promising natural agent for supplementing the current anti-cancer drugs used for the treatment of GBM.
摘要：
胶质母细胞瘤（GBM）是最具侵袭性的癌症之一，以抗氧化剂水平降低为特征。有证据表明，阿魏酸（FA），一种在蔬菜和水果中特别丰富的天然抗氧化剂，可能是GBM治疗的有希望的候选人。由于FA显示出高不稳定性，损害了其治疗应用，它已被封装到纳米结构脂质载体（NLCs）中，以提高其在大脑中的生物利用度。已经证明，组织转谷氨酰胺酶（TG2）是一种参与许多生理和病理过程的多功能蛋白，包括癌症.TG2还参与与转移形成和耐药性相关的GBM。因此,评估TG2的表达水平及其细胞定位对于评估FA对GBM癌症的抗癌作用很重要。我们的结果表明，在U87-MG癌细胞系中用游离FA和FA-NLCs治疗会不同程度地改变TG2的定位和表达水平。在用游离FA处理的细胞中，TG2在细胞质和细胞核中都有表达，虽然用FA-NLCs处理显示该蛋白仅位于胞质溶胶中，发挥其促凋亡作用。因此,我们的数据表明,NLCs中负载的FA可能是一种有前景的天然药物,用于补充目前用于治疗GBM的抗癌药物.
