RESUMEN
The regulation of metastasis-related cellular aspects of two structurally similar AGIs from prunes tea infusion, with different molar masses, was studied in vitro against Triple Wild-Type metastatic melanoma (TWM) from murine and human origin. The higher molar mass AGI (AGI-78KDa) induced TWMs cells death and, in murine cell line, it decreased some metastasis-related cellular processes: invasiveness capacity, cell-extracellular matrix interaction, and colonies sizes. The lower molar mass AGI (AGI-12KDa) did not induce cell death but decreased TWMs proliferation rate and, in murine cell line, it decreased cell adhesion and colonies sizes. Both AGIs alter the clonogenic capacity of human cell line. In spite to understand why we saw so many differences between AGIs effects on murine and human cell lines we performed in silico analysis that demonstrated differential gene expression profiles between them. Complementary network topological predictions suggested that AGIs can modulate multiple pathways in a specie-dependent manner, which explain differential results obtained in vitro between cell lines. Our results pointed to therapeutic potential of AGIs from prunes tea against TWMs and showed that molecular weight of AGIs may influence their antitumor effects.
Asunto(s)
Galactanos , Melanoma , Humanos , Ratones , Animales , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/metabolismo , Peso Molecular , Té , Línea Celular TumoralRESUMEN
Advanced melanoma patients that are not included in common genetic classificatory groups lack effective and safe therapeutic options. Chemotherapy and immunotherapy show unsatisfactory results and devastating adverse effects for these called triple wild-type patients. New approaches exploring the intrinsic antitumor properties of gold nanoparticles might reverse this scenario as a safer and more effective alternative. Therefore, we investigated the efficacy and safety of a composite made of gum arabic-functionalized gold nanorods (GA-AuNRs) against triple wild-type melanoma. The natural polymer gum arabic successfully stabilized the nanorods in the biological environment and was essential to improve their biocompatibility. In vivo results obtained from treating triple wild-type melanoma-bearing mice showed that GA-AuNRs remarkably reduced primary tumor growth by 45%. Furthermore, GA-AuNRs induced tumor histological features associated with better prognosis while also reducing superficial lung metastasis depth and the incidence of intrapulmonary metastasis. GA-AuNRs' efficacy comes from their capacity to reduce melanoma cells ability to invade the extracellular matrix and grow into colonies, in addition to a likely immunomodulatory effect induced by gum arabic. Additionally, a broad safety investigation found no evidence of adverse effects after GA-AuNRs treatment. Therefore, this study unprecedentedly reports GA-AuNRs as a potential nanomedicine for advanced triple wild-type melanomas.