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Publications

Journal Article Epublish

PubMed: 36987163 DOI: 10.3390/polym15061382

Assessing the Antitumor Potential of Variants of the Extracellular Carbohydrate Polymer from Δ Mutant.

Polymers (Basel) 15(6)

Authors: Rita Mota, Raquel T Lima, Carlos Flores, Juliana F Silva, Beatriz Cruz, Bárbara Alves, Marta T Pinto, Alessandra Adessi, Sara B Pereira, Roberto De Philippis, Paula Soares, Paula Tamagnini

Affiliations

  • i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
  • IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
  • IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
  • FMUP - Department of Pathology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
  • ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
  • FCUP - Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal.
  • School of Allied Health Sciences of Polytechnic Institute of Porto, Rua Dr. António Bernardino de Almeida 400, 4200-072 Porto, Portugal.
  • i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
  • DAGRI - Department of Agriculture, Food, Environment and Forestry, University of Florence, Via Maragliano 77, 50144 Firenze, Italy.

Abstract

Cancer is a leading cause of death worldwide with a huge societal and economic impact. Clinically effective and less expensive anticancer agents derived from natural sources can help to overcome limitations and negative side effects of chemotherapy and radiotherapy. Previously, we showed that the extracellular carbohydrate polymer of a Δ overproducing mutant displayed a strong antitumor activity towards several human tumor cell lines, by inducing high levels of apoptosis through p53 and caspase-3 activation. Here, the Δ polymer was manipulated to obtain variants that were tested in a human melanoma (Mewo) cell line. Our results demonstrated that high molecular mass fractions were important for the polymer bioactivity, and that the reduction of the peptide content generated a variant with enhanced antitumor activity. This variant, and the original Δ polymer, were further tested using the chick chorioallantoic membrane (CAM) assay. Both polymers significantly decreased xenografted CAM tumor growth and affected tumor morphology, by promoting less compact tumors, validating their antitumor potential . This work contributes with strategies for the design and testing tailored cyanobacterial extracellular polymers and further strengths the relevance of evaluating this type of polymers for biotechnological/biomedical applications.

MeSH

Carbohydrates, Polymers, Cells, Neoplasms, Cell Line, Cyanobacteria, Caspase 3

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