Anti-Tumor Activity of Silver Bionanoparticles in Anaplastic Thyroid Cancer cells

AGUSTINA JAROSZEWSKI, 1 MARIA VICTORIA BRAICA, 1 CLAUDIA GABRIELA PELLIZAS, 4 PAULINA LAURA PÁEZ, 2 JACK ZHU, 3 SHEUE-YANN CHENG AND 1 LAURA FOZZATTI

Curitiba

Congreso; XIX Latin American Thyroid Society Congress; 2023

Introduction: Anaplastic thyroid cancer (ATC) is a highly aggressive type of thyroid cancer(TC). Currently, no effective target treatments are available that can improve overallsurvival, with ATC representing a major clinical challenge because of its remarkablelethality. A novel therapeutic modality for the treatment is therefore urgently needed.Recently, metal nanoparticles have been extensively explored in a variety of biologicalapplications because of its versatile properties. Among them, silver bionanoparticles(AgNPs) have emerged as an useful agent for cancer treatment. AgNPs were previouslybiosynthesized by Pseudomonas aeruginosa culture supernatant with an importantmicrobicide activity. However, their anti-tumor impact in ATC cells is not known.Aim: In this study we explored the anti-tumor effects of AgNPs on human ATC cellsderived from patient tumors.Methods: ATC cells (8505C, C643, THJ-11T and THJ-16T cells) were treated with AgNPs(0.2?1.25 pM), for 24h. The anti-cancer potential of AgNPs was investigated by the MTTassay. Differentially expressed genes (DEGs) were detected by transcriptome sequencing(RNA-seq). The functional properties of DEGs were characterized by Reactome pathwayanalyses. Additionally, apoptosis in ATC cells was examined through the expression ofcleaved caspase-3 and cleaved PARP by Western blot assay.Results: The exposure to AgNPs produced changes in ATC cell lines morphology andsignificantly decreased cell viability. DEG analysis between control and 0.75pM AgNPs-treated 8505c cells revealed 2242 DEGs, including 1501 upregulated genes and 741downregulated genes. Among these DEGs, IL1A, MT2A, CTSL, MT1X, SBSN, SMAD7,MMP10, CRYAB, SERPINB2, SERPINE1, TPH2, RASD1, HSPA6, HSPA1A, ARC were identifiedas the top DEGs in AgNPs treated ATC cells. Reactome analysis revealed that "Attenuationphase", "HSF1-dependent transactivation", "NGF-stimulated transcription", "HSF1activation", "Metallothioneins bind metals", "Nuclear Events", "Response to metal ions","Antagonism of Activing by Follistatin", "Interleukin-33 signaling", and "Activation ofMatrix" were among the top enriched pathways in our AgNPs treatment comparisons.Additionally, AgNPs induced a significant increase in the expression levels of apoptoticmarkers cleaved caspase-3 and cleaved PARP in 8505c cells, as compared with untreatedcontrol cells.Conclusions: Our results indicate that the AgNPs have remarkable in vitro anti-tumorefficacy in ATC cells and provide an understanding of the potential genes and pathwaysinvolved in these effects. Therefore, AgNPs represent promising candidates as noveltherapeutic agents for ATC. Validation of the gene expression profiles, and elucidation oftheir molecular mechanisms are being performed.