Tarin-Loaded Nanoliposomes Activate Apoptosis and Autophagy and Inhibit the Migration of Human Mammary Adenocarcinoma
Raiane Vieira Cardoso1, Patricia Ribeiro Pereira1, Cyntia Silva Freitas1
1Departamento de Bioquímica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Tarin, a lectin from Colocasia esculenta, when encapsulated in nanoliposomes, effectively combats breast cancer cells by inducing apoptosis and autophagy. This formulation shows reduced toxicity to healthy cells and inhibits cancer cell migration.
Area of Science:
- Biochemistry
- Cell Biology
- Nanotechnology
Background:
- Tarin, a lectin from Colocasia esculenta, exhibits immunomodulatory, anticancer, and antimetastatic properties.
- This 47 kDa protein is a potential therapeutic candidate for human breast cancer.
- Encapsulating tarin in pegylated nanoliposomes enhances its efficacy against human mammary adenocarcinoma cells, including MDA-MB-231 lineage.
Purpose of the Study:
- To investigate the mechanisms underlying the anticancer and antimetastatic effects of nano-encapsulated tarin.
- To assess the safety of nano-encapsulated tarin on healthy tissues.
- To evaluate the impact of nano-encapsulated tarin on cancer cell migration.
Main Methods:
- MDA-MB-231 cells were treated with nano-encapsulated tarin (72 μg/mL) for up to 48 hours.
- Flow cytometry and transmission electron microscopy (TEM) were used to analyze cellular mechanisms.
- Resazurin viability assay and scratch assays were employed to assess safety and migration inhibition, respectively.
Main Results:
- Ultrastructural analysis revealed autophagosome accumulation and organelle damage, indicating autophagy-dependent cell death.
- Flow cytometry showed increased acidic vacuolar organelles, apoptotic cells, activated caspase-3/7, and G0/G1 cell cycle arrest.
- Nano-encapsulated tarin demonstrated no toxicity to healthy fibroblasts, inhibited MDA-MB-231 cell migration, and delayed cell movement compared to free tarin.
Conclusions:
- Nanoliposome formulation enables sustained delivery of tarin, leading to potent antitumoral and anti-migration effects with no observed toxicity to healthy cells.
- The antitumorigenic mechanisms of tarin involve the activation of apoptotic and autophagic pathways, caspase-3/7 activation, and cell cycle arrest.
- Nano-encapsulated tarin represents a promising therapeutic strategy for breast cancer treatment.
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