Green-synthesized Desertifilum silver nanoparticles induce BAX/BCL-2 mediated apoptosis in Ehrlich carcinoma

Abstract

Green and biogenic silver nanoparticles (AgNPs) are widely researched as anticancer treatments; nevertheless, in vivo data on cyanobacteria-derived formulations and their apoptotic mechanisms are limited. To assess the antitumor activity, hematological safety, and apoptosis-related pathways of Desertifilum tharense-derived AgNPs, provided either independently or in conjunction with Desertifilum exopolysaccharides (EPS), in a mouse Ehrlich cell carcinoma (ECC) model. Male Swiss albino mice were assigned to five groups: healthy control, AgNP toxicity control, tumor control, AgNP-treated tumor, and AgNPs + EPS-treated tumor. Endpoints encompassed body weight, thigh tumor volume, hematological profiling, histology, immunohistochemistry identification of cleaved caspase 3, and real-time PCR quantification of BAX, BCL-2, and caspase 3 mRNA, utilizing the BAX/BCL-2 ratio as an indicator of apoptotic equilibrium. Tumor control subjects exhibited significant increases in body weight and tumor volume, along with anemia, leukocytosis, and altered leukocyte differentials. The AgNP-treated groups had markedly decreased tumor sizes and partial restoration of hematological parameters, whereas healthy mice treated solely with AgNP maintained values within physiological limits. Tumor sections from treated mice exhibited significant necrosis and a treatment-dependent increase in cleaved caspase 3 staining, most apparent and widespread in the AgNPs + EPS group. Gene expression analysis demonstrated a considerable upregulation of BAX and caspase 3, alongside a downregulation of BCL-2 in treated tumors, with the combination formulation exhibiting the highest BAX/BCL-2 ratio, indicative of pronounced activation of mitochondria-mediated apoptosis. Desertifilum-derived AgNPs demonstrate in vivo antitumor efficacy against ECC with satisfactory hematological safety and induce caspase 3 dependent, mitochondria-mediated apoptosis via regulation of the BAX/BCL-2 axis. The co-administration with EPS enhances the pro-apoptotic gene and protein profile, endorsing cyanobacteria-based AgNP/EPS systems as viable candidates for future nano-based cancer therapies.