Synthesis of CEG-AgNPs as a Promising MMPs/COX-2/Bcl-2 Signaling Pathway Modulator in BaP-Induced Lung Carcinoma

Abstract

Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids. It's hydrophobic properties and poor solubility in water, polymeric micellar systems exhibited improved antitumor efficacy because of a better solubilization and targeting after local and/or systemic administration. The aim of the present work was to evaluate the anticancer activity of CEG-AgNPs against benzo[a]pyren (BaP)-induced lung carcinoma. CEG-AgNPs was prepared, characterized and evaluated for its cytotoxic activity against A549 lung carcinoma cell line. Also, the anticancer activity of CEG-AgNPs (70.25 mg/kg) against BaP-induced lung carcinoma was evaluated in vivo, using 30 adult mice for 43 days. IC50 of CEG-AgNPs against A549 lung carcinoma cell line were approximately 94.47 µg/mL. Administration of BaP (50 mg/kg b.w.) to mice induced lung carcinoma with a significant increase in lung MMP-2, MMP-9, MMP-12, MDA, IL-6 and NF-κB as well as significant decreased in lung CAT, GPx and GSH level. Also, treatment with BaP produced significant increase in lung VEGF-C, COX-2 and Bcl-2 gene expression as compared to control group. Daily oral administration of CEG-AgNPs to mice treated with BaP showed a significant protection against-induced increase in lung MMP-2, MMP-9, MMP-12, MDA, IL-6 and NF-κB levels. The treatment also resulted in a significant increase in lung CAT, GPx and GSH level. In addition, the CEG-AgNPs could inhibit lung VEGF-C, COX-2 and Bcl-2 gene expression as compared to BaP treated mice. The histological and MRI examination showed that a significant normalization has been observed through in CEG-AgNPs treated mice. The biochemical, histological and MRI results showed that CEG-AgNPs have potent anticancer activity against BaP-induced lung carcinoma through modulating multiple cellular behaviours and signaling pathways leading to the suppression of adaptive immune responses.