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

AGUSTINA JAROSZEWSKI; BRAICA, MARIA VICTORIA; PELLIZAS, CLAUDIA GABRIELA; PAEZ PAULINA LAURA; JACK ZHU; CHENG SHEUE-YANN; FOZZATTI, LAURA

Curitiba

Congreso; XIX Latin American Thyroid 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 overall survival, with ATC representing a major clinical challenge because of its remarkable lethality. A novel therapeutic modality for the treatment is therefore urgently needed. Recently, metal nanoparticles have been extensively explored in a variety of biological applications because of its versatile properties. Among them, silver bionanoparticles (AgNPs) have emerged as an useful agent for cancer treatment. AgNPs were previously biosynthesized by Pseudomonas aeruginosa culture supernatant with an important microbicide activity. However, their anti-tumor impact in ATC cells is not known.Aim: In this study we explored the anti-tumor effects of biogenic AgNPs on human ATC cells derived 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 MTT assay. Differentially expressed genes (DEGs) were detected by transcriptome sequencing (RNA-seq). The functional properties of DEGs were characterized by Reactome pathway analyses. Additionally, apoptosis in ATC cells was examined through the expression of cleaved caspase-3 and cleaved PARP by Western blot assay. Results: The exposure to AgNPs produced changes in ATC cell lines morphology and significantly decreased cell viability. DEG analysis between control and 0.75pM AgNPs-treated 8505c cells revealed 2242 DEGs, including 1501 upregulated genes and 741 downregulated genes. Among these DEGs, IL1A, MT2A, CTSL, MT1X, SBSN, SMAD7, MMP10, CRYAB, SERPINB2, SERPINE1, TPH2, RASD1, HSPA6, HSPA1A, ARC were identified as the top DEGs in AgNPs treated ATC cells. Reactome analysis revealed that "Attenuation phase", "HSF1-dependent transactivation", "NGF-stimulated transcription", "HSF1 activation", "Metallothioneins bind metals", "Nuclear Events", "Response to metal ions", "Antagonism of Activing by Follistatin", "Interleukin-33 signaling", and "Activation of Matrix" were among the top enriched pathways in our AgNPs treatment comparisons. Additionally, AgNPs induced a significant increase in the expression levels of apoptotic markers cleaved caspase-3 and cleaved PARP in 8505c cells, as compared with untreated control cells. Conclusions: Our results indicate that the biogenic AgNPs have remarkable in vitro anti-tumor efficacy in ATC cells and provide an understanding of the potential genes and pathways involved in these effects. Therefore, AgNPs represent promising candidates as novel therapeutic agents for ATC. Validation of the gene expression profiles, and elucidation of their molecular mechanisms are being performed.