# Fucoidan from Lessonia trabeculata Induces Apoptosis through Caspase Dependent and Caspase-Independent Activation in 4T1 Breast Adenocarcinoma In Vitro

**Authors:** Raisa Teresa Cruz Riquelme, Erasmo Honorio Colona-Vallejos, Libertad Alzamora-Gonzales, Rosa María Condori Macuri

PMC · DOI: 10.3390/md22060251 · Marine Drugs · 2024-05-29

## TL;DR

Fucoidan from Lessonia trabeculata induces apoptosis in breast cancer cells through both caspase-dependent and caspase-independent pathways.

## Contribution

This study demonstrates FLt's dual apoptotic mechanisms in 4T1 breast cancer cells.

## Key findings

- FLt induces apoptosis via caspase-dependent and caspase-independent pathways in 4T1 cells.
- FLt reduces antiapoptotic gene expression and increases proapoptotic gene expression.
- DNA fragmentation and annexin V results suggest both apoptotic and necrotic cell death.

## Abstract

Experiments conducted on triple-negative breast cancer have shown that fucoidan from Lessonia trabeculata (FLt) exhibits cytotoxic and antitumor properties. However, further research is necessary to gain a complete understanding of its bioactivity and level of cytotoxicity. The cytotoxic effect of FLt was determined by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was analyzed using annexin V and caspase 3/7 staining kit and DNA fragmentation. In addition, transcriptional expression of antiapoptotic (Bcl-2 and XIAP) and proapoptotic (caspase 8, caspase 9, and AIF) genes were analyzed in TNBC 4T1 cells. After 72 h of culture, the IC50 for FLt was 561 μg/mL, while doxorubicin (Dox) had an IC50 of 0.04 μg/mL. In addition, assays for FLt + Dox were performed. Annexin V and caspase 3/7 revealed that FLt induces early and late-stage apoptosis. DNA fragmentation results support necrotic death of 4T1 cells. Similarly, transcripts that prevent cell death were decreased, while transcripts that promote cell death were increased. This study showed that FLt induces apoptosis by both caspase-dependent and caspase-independent mechanisms. These findings suggest that FLt may have potential applications in breast cancer treatment. Further research will provide more information to elucidate the mechanism of action of FLt.

## Linked entities

- **Genes:** BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], XIAP (X-linked inhibitor of apoptosis) [NCBI Gene 331], casp8 (caspase 8, apoptosis-related cysteine peptidase) [NCBI Gene 58022], Casp9 (caspase 9) [NCBI Gene 12371], AIFM1 (apoptosis inducing factor mitochondria associated 1) [NCBI Gene 9131]
- **Chemicals:** doxorubicin (PubChem CID 31703)
- **Diseases:** breast cancer (MONDO:0004989)
- **Species:** Lessonia trabeculata (taxon 169772)

## Full-text entities

- **Genes:** Anxa5 (annexin A5) [NCBI Gene 11747] {aka Anx5, CPB-I}, Xiap (X-linked inhibitor of apoptosis) [NCBI Gene 11798] {aka 1110015C02Rik, Aipa, Api3, Birc4, IAP3, ILP-1}, Casp9 (caspase 9) [NCBI Gene 12371] {aka APAF-3, CASP-9, Caspase-9, ICE-LAP6, Mch6}, Aifm1 (apoptosis-inducing factor, mitochondrion-associated 1) [NCBI Gene 26926] {aka AIF, AIFsh2, Hq, Pdcd8}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Casp8 (caspase 8) [NCBI Gene 12370] {aka CASP-8, FLICE, MACH, Mch5}
- **Diseases:** triple-negative breast cancer (MESH:D064726), Breast Adenocarcinoma (MESH:D001943), necrotic death (MESH:D003643), cytotoxic (MESH:D064420)
- **Chemicals:** MTT (MESH:C070243), Fucoidan (MESH:C007789), 2,5-diphenyl-2H-tetrazolium bromide (-), Dox (MESH:D004317)
- **Species:** Lessonia trabeculata (species) [taxon 169772]
- **Cell lines:** 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11205089/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC11205089/full.md

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Source: https://tomesphere.com/paper/PMC11205089