负载塔林的纳米脂质体激活细胞凋亡和自噬并抑制人乳腺癌细胞的迁移。
Tarin-Loaded Nanoliposomes Activate Apoptosis and Autophagy and Inhibit the Migration of Human Mammary Adenocarcinoma Cells.
发表日期:2023
作者:
Raiane Vieira Cardoso, Patricia Ribeiro Pereira, Cyntia Silva Freitas, Érika Bertozzi de Aquino Mattos, Anna Victoria De Freitas Silva, Victor do Valle Midlej, Mauricio Afonso Vericimo, Carlos Adam Conte-Júnior, Vania Margaret Flosi Paschoalin
来源:
International Journal of Nanomedicine
摘要:
Tarin 是一种从 Colocasia esculenta 中纯化出来的凝集素,可促进体外和体内的免疫调节作用,并有望对人腺癌细胞产生抗癌和抗转移作用。这使得这种 47 kDa 的蛋白质成为对抗人类乳腺癌的天然候选者,人类乳腺癌是女性死亡的主要原因。封装在聚乙二醇化纳米脂质体中的 Tarin 在控制包含 MDA-MB-231 细胞的乳腺癌谱系的增殖方面显示出更高的有效性。通过在 72 ℃下用纳米封装的 Tarin 处理 MDA-MB-231 细胞,研究了抗癌和抗转移反应的机制。通过流式细胞术和透射电子显微镜 (TEM) 检测 μg/mL 长达 48 小时。还通过刃天青活力测定评估了纳米封装塔林对健康组织的安全性,并通过划痕试验评估了纳米封装塔林对细胞迁移的影响。暴露于纳米封装塔林的 MDA-MB-231 细胞的超微结构分析揭示了纳米封装塔林的积累自噬体和受损的细胞器,与自噬依赖性细胞死亡相容。另一方面,流式细胞术研究检测到酸性液泡细胞器(一种晚期自噬体特征)的出现增加,以及凋亡细胞、激活的 caspase-3/7 和细胞周期停滞在 G0/G1 的增加。与暴露于游离焦油酸的细胞活力降低相反,在暴露于焦油酸纳米胶囊后,在健康成纤维细胞中没有观察到有害影响。纳米封装的 tarin 抑制了 MDA-MB-231 细胞的迁移,与游离 tarin 相比,其运动延迟了 24 小时。纳米脂质体制剂以延迟和持续的方式递送 tarin,迟来且有效的抗肿瘤和抗肿瘤作用证明了这一点。 -对腺癌细胞有迁移作用,对健康细胞没有毒性。尽管需要进一步研究才能充分了解抗肿瘤 tarin 机制,但凋亡和自噬机制以及 caspase-3/7 途径的激活以及细胞周期停滞可能构成这些机制的一部分。© 2023 Cardoso 等人。
Tarin, a lectin purified from Colocasia esculenta, promotes in vitro and in vivo immunomodulatory effects allied to promising anticancer and antimetastatic effects against human adenocarcinoma mammary cells. This makes this 47 kDa-protein a natural candidate against human breast cancer, a leading cause of death among women. Tarin encapsulated in pegylated nanoliposomes displays increased effectiveness in controlling the proliferation of a mammary adenocarcinoma lineage comprising MDA-MB-231 cells.The mechanisms enrolled in anticancer and antimetastatic responses were investigated by treating MDA-MB-231 cells with nano-encapsulated tarin at 72 μg/mL for up to 48h through flow cytometry and transmission electron microscopy (TEM). The safety of nano-encapsulated tarin towards healthy tissue was also assessed by the resazurin viability assay, and the effect of nanoencapsulated tarin on cell migration was evaluated by scratch assays.Ultrastructural analyses of MDA-MB-231 cells exposed to nanoencapsulated tarin revealed the accumulation of autophagosomes and damaged organelles, compatible with autophagy-dependent cell death. On the other hand, the flow cytometry investigation detected the increased occurrence of acidic vacuolar organelles, a late autophagosome trait, along with the enhanced presence of apoptotic cells, activated caspase-3/7, and cell cycle arrest at G0/G1. No deleterious effects were observed in healthy fibroblast cells following tarin nanoencapsulated exposition, in contrast to reduced viability in cells exposed to free tarin. The migration of MDA-MB-231 cells was inhibited by nano-encapsulated tarin, with delayed movement by 24 h compared to free tarin.The nanoliposome formulation delivers tarin in a delayed and sustained manner, as evidenced by the belated and potent antitumoral and anti-migration effects on adenocarcinoma cells, with no toxicity to healthy cells. Although further investigations are required to fully understand antitumorigenic tarin mechanisms, the activation of both apoptotic and autophagic machineries along with the caspase-3/7 pathway, and cell cycle arrest may comprise a part of these mechanisms.© 2023 Cardoso et al.