Evaluation of hepatic cancer stem cells (CD, CD, and CD) induced by diethylnitrosamine in male rats and treatment with biologically synthesized silver nanoparticles.

Background: Cancer stem cells (CSCs) play a critical role in the initiation and heterogeneity of a variety of cancers due to their pluripotent nature and capacity for asymmetric cell division. Therefore, uncovering the carcinogens that increase the CSC population in target tissues is crucial for understanding the genesis of cancer. The therapeutic potential of Operculina turpethum (OT) derived silver nanoparticles (AgNPs) was assessed in diethylnitrosamine (DEN)-induced CSC populations; CD73+, CD44+, and CD90 + of hepatic tissues in male rats.

Methods: Histopathology, fluorescence-activated cell sorting (FACS), and RT-qPCR were performed on the control, DEN, DEN + AgNPs, and AgNPs-treated groups. AgNPs were characterized by FTIR, EDX, XRD, and SEM.

Results: AgNPs were confirmed by intense surface plasmon resonance at 425 nm. Antioxidants, the reducing sugars responsible for Ag reduction and subsequent conjugate formation with nanoparticles, were confirmed by vibrational spectra. The spherical morphology, composition, and conjugation of silver nanoparticles to phytoconstituents with partially crystalline, face-centered cubic structure were established through SEM, EDX spectrum, and XRD, respectively. Disrupted tissue architecture, cell enlargement, mild pleomorphism, and expanded central veins were observed in hepatic tissues of DEN-treated animals. However, a moderate inflammatory response was observed in the DEN + AgNPs-treated group. CSC populations were significantly increased in the DEN-treated group, but decreased with AgNPs-treatment. The mRNA expression levels of CD90, CD44, and CD73 genes were significantly up-regulated in the DEN-treated group compared to control group however, in DEN + AgNPs and AgNPs groups it were similar to control group.

Conclusion: All together, DEN-induced the hepatic CSC cell populations and the OT mediated AgNPs have therapeutic potential to attenuate the harmful effects of DEN. This study provides evidenced that OT-synthesised AgNPs may be considered as a therapeutic agent for liver related malignancies.