Astaxanthin induces autophagy and apoptosis in murine melanoma B16F10-Nex2 cells and exhibits antitumor activity in vivo

Abstract

Countless efforts have been made to prevent and suppress the formation and spread of melanoma. Natural astaxanthin (AST; extracted from the alga Haematococcus pluvialis) showed an antitumor effect on various cancer cell lines due to its interaction with the cell membrane. This study aimed to characterize the antitumor effect of AST against B16F10-Nex2 murine melanoma cells using cell viability assay and evaluate its mechanism of action using electron microscopy, western blotting analysis, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and mitochondrial membrane potential determination. Astaxanthin exhibited a significant cytotoxic effect in murine melanoma cells with features of apoptosis and autophagy. Astaxanthin also decreased cell migration and invasion in vitro assays at subtoxic concentrations. In addition, assays were conducted in metastatic cancer models in mice where AST significantly decreased the development of pulmonary nodules. In conclusion, AST has cytotoxic effect in melanoma cells and inhibits cell migration and invasion, indicating a promising use in cancer treatment.

Keywords:

• Antitumor activity
• apoptosis
• astaxanthin
• autophagy
• cell migration
• invasion
• melanoma
• metastasis

Acknowledgements

We thank Dr. Rita Sinigaglia Coimbra (UNIFESP) for her support in electron microscopy.

Author contributions

All authors contributed to writing the manuscript and approved its final version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was funded by Fundação de Amparo ao Ensino e Pesquisa do Estado de São Paulo [FAPESP 2015/05980-9, 2018/11972-7, and 2018/25747-5], Conselho Nacional de Pesquisa (CNPq) [312020/2019-8], and Centro de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). DCM is a recipient of a Productivity Fellowship [CNPq: 314811/2021].