Therapeutic potential of pectin from passion fruit peel: Antimelanoma effect in murine and human pre-clinical models

Melanoma is the deadliest form of skin cancer and still has a poor prognosis when in metastatic stage. Currently available treatments often lead to resistance development and several adverse effects. Plant-derived polysaccharides have demonstrated diverse immunological and antitumor activities. This study explored the immunomodulatory and antimelanoma potential of an homogalacturonan from passion fruit peel (HG-PFP). HG-PFP induced a pro-inflammatory phenotype in macrophages, enhancing nitric oxide, reactive oxygen species, and cytokine release. In B16-F10 melanoma-bearing mice, HG-PFP (50 mg/kg) reduced tumor growth by 60% and lung colonization by 54%, with no adverse effects. Even though the tumor microenvironment macrophage population was not altered by the treatment, monocyte chemoattractant protein-1 (MCP-1) levels were changed in both subcutaneous tumor and lung colonization models. Considering melanoma high heterogeneity and subtypes and to further expand HG-PFP treatment effects investigation, we evaluated human preclinical melanoma model bearing melanoma driver mutations (BRAF, NRAS, and NF1), using patient-derived organoids (PDOs). HG-PFP treatment inhibited NF1 mutant PDOs growth by reducing cells viability and impaired organoids formation and growth in NRAS mutant samples, while showing no effects in BRAF mutant samples. Taking together these findings provide a preclinical perspective on therapeutic potential of HG-PFP across different melanoma subtypes.