Trachyspermum ammi seed extract modulated nanosilver as a transformative agent for anticancer activity

Abstract

The present study focused on evaluating the anticancer potential of biosynthesized Trachyspermum ammi- mediated silver nanoparticles (TA-AgNPs) using both in vitro and in vivo approaches. TA-AgNPs were synthesized through a rapid, eco-friendly, and cost-effective green synthesis method and assessed for their suitability in biomedical applications. In vitro anticancer activity was examined against the A431 epidermal skin cancer cell line using the Alamar Blue assay. In vivo anticancer activity was evaluated using a two-stage skin carcinogenesis model induced by 7,12-dimethylbenz [a]-anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in Swiss albino mice. Various tumor parameters, including tumor incidences, tumor yield, tumor burden, tumor size, and average latent period, were assessed. Additionally, antioxidant status was analyzed through superoxide dismutase (SOD) activity. This was further supported by histopathological analysis and estimation of serum interleukin-6 (IL-6) levels. TA-AgNPs demonstrated dose-dependent cytotoxic activity against A431 skin cancer cells in vitro (2.5–25 μg/mL). In vivo, TA-AgNPs treatment markedly reduced tumor incidence, yield, and burden while delaying tumor onset compared to the carcinogen control (Group I: 181.6 pg/mg), with the continuous treatment (Group IIc) providing the most pronounced protection. TA-AgNPs enhanced antioxidant defense, with Group IIc showing a highly significant elevation in SOD activity (55.41 U/50 µL) compared to Groups IIa (45.22 U/50 µL) and IIb (43.34 U/50 µL). Serum IL-6 levels remained elevated across carcinogen-treated groups (Group I: 181.6 pg/mg; Groups IIa–IIc: 162.8–198.5 pg/mg) compared to untreated baseline controls (63.5 pg/mg), reflecting the persistent pro-inflammatory microenvironment established during DMBA/TPA-mediated tumorigenesis. Importantly, TA-AgNPs administered alone (Group III: 65.2 pg/mg) caused no significant IL-6 elevation, demonstrating their baseline biocompatibility and lack of inherent immunogenicity. Histopathology confirmed preserved epithelial architecture in TA-AgNP-treated groups. These findings indicate that TA-AgNPs exert potent chemopreventive effects primarily through antioxidant enhancement and direct tumor growth mitigation rather than systemic IL-6 suppression.