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纳米封装的芋头凝集素可穿过体外血脑屏障,诱导细胞凋亡和自噬,并抑制人U-87 MG胶质母细胞瘤细胞的迁移。

Nano-Encapsulated Taro Lectin Can Cross an in vitro Blood-Brain Barrier, Induce Apoptosis and Autophagy and Inhibit the Migration of Human U-87 MG Glioblastoma Cells.

作者信息

Cardoso Raiane Vieira, Pereira Patricia Ribeiro, Freitas Cyntia Silva, De Freitas Silva Anna Victoria, Midlej Victor, Conte-Júnior Carlos Adam, Paschoalin Vania Margaret Flosi

机构信息

Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.

出版信息

Int J Nanomedicine. 2025 Apr 29;20:5573-5591. doi: 10.2147/IJN.S511506. eCollection 2025.

DOI:10.2147/IJN.S511506
PMID:40321803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12049682/
Abstract

BACKGROUND

Tarin, purified from taro (), promotes anticancer effect against glioblastoma cells, a heterogeneous and aggressive primary central nervous system tumor and one of the most challenging tumors for oncotherapy. If able to overcome the blood-brain barrier (BBB), tarin may comprise a natural defense against glioblastomas in a context of the development of novel drugs to control these malignant cell proliferations.

METHODS

The anticancer effects of nano-encapsulated tarin were tested against U-87 MG cells and the molecular mechanisms involved in cell proliferation control were assessed by flow cytometry and transmission electron microscopy (TEM) analyses. The scratch assay was performed to investigate cell migration capacity, while nano-encapsulated tarin transport across the BBB was tested on the hCMEC/D3 endothelial cell line.

RESULTS

Nano-encapsulated tarin induced autophagy in U-87 MG cells, characterized by the presence of autophagosomes as revealed by TEM and corroborating the flow cytometry analysis employing acridine orange. Additional ultrastructural changes, such as mitochondrial swelling, were also observed. The presence of apoptotic cells and caspase 3/7 activation indicate that nano-encapsulated tarin may also induce cell death through apoptosis. Glioblastoma cell proliferation was arrested in the G2/M cell cycle phase, and cell migration was delayed. Reduced cell proliferation and glioblastoma cell migration inhibition were significant, as tarin was efficiently transported across the BBB during in vitro assays.

CONCLUSION

Nano-encapsulated tarin may be effectively employed to inhibit glioblastoma cell proliferation and migration, as this novel formulation can overcome the BBB and induces carcinoma cell apoptosis and autophagy. Furthermore, nano-encapsulated tarin may comprise a novel chemotherapeutic agent against different tumoral lines, as it is able to control glioblastoma tumor proliferation by the same molecular mechanisms previously reported for breast adenocarcinomas. Additional studies should be carried out to clarify if nano-encapsulated tarin has a general effect on distinct carcinoma lines.

摘要

背景

从芋头中提纯的塔林可增强对胶质母细胞瘤细胞的抗癌作用,胶质母细胞瘤是一种异质性且侵袭性强的原发性中枢神经系统肿瘤,也是肿瘤治疗中最具挑战性的肿瘤之一。若塔林能够突破血脑屏障,那么在开发控制这些恶性细胞增殖的新型药物的背景下,它可能成为对抗胶质母细胞瘤的一种天然防御手段。

方法

测试了纳米包裹的塔林对U - 87 MG细胞的抗癌作用,并通过流式细胞术和透射电子显微镜(TEM)分析评估了细胞增殖控制中涉及的分子机制。进行划痕试验以研究细胞迁移能力,同时在hCMEC/D3内皮细胞系上测试纳米包裹的塔林穿越血脑屏障的转运情况。

结果

纳米包裹的塔林在U - 87 MG细胞中诱导自噬,TEM显示存在自噬体,这与使用吖啶橙的流式细胞术分析结果一致。还观察到其他超微结构变化,如线粒体肿胀。凋亡细胞的存在和半胱天冬酶3/7的激活表明纳米包裹的塔林也可能通过凋亡诱导细胞死亡。胶质母细胞瘤细胞增殖在G2/M细胞周期阶段被阻滞,细胞迁移延迟。在体外试验中,由于塔林能有效穿越血脑屏障,细胞增殖减少和胶质母细胞瘤细胞迁移抑制显著。

结论

纳米包裹的塔林可有效用于抑制胶质母细胞瘤细胞的增殖和迁移,因为这种新型制剂能够突破血脑屏障并诱导癌细胞凋亡和自噬。此外,纳米包裹的塔林可能构成一种针对不同肿瘤细胞系的新型化疗药物,因为它能够通过先前报道的对乳腺腺癌相同的分子机制来控制胶质母细胞瘤的肿瘤增殖。应开展更多研究以阐明纳米包裹的塔林对不同癌细胞系是否具有普遍作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/9eeff8c5abfe/IJN-20-5573-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/0f385c52f177/IJN-20-5573-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/2490a37d93a7/IJN-20-5573-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/48b27ff01697/IJN-20-5573-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/976a565a860c/IJN-20-5573-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/d449ce2f24b0/IJN-20-5573-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/3df96707024e/IJN-20-5573-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4807/12049682/9eeff8c5abfe/IJN-20-5573-g0009.jpg

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