Open AccessSynthesis of CEG-AgNPs as a Promising MMPs/COX-2/Bcl-2 Signaling Pathway Modulator in BaP-Induced Lung Carcinoma
Author(s) -
Ahmed Emara,
Ahmed M. Darwesh,
Mohamed A. Mostafa,
Ahmed A. Ahmed,
Khaled W. Rashad,
Abdullah M Said,
Abdelrahman E. Elsebaay,
Khaled M. Nasser,
Abdelrehem S. Amin,
Mohamed S. Gamil,
Foad H. Mohamed,
Mohamed Ahmed,
Diana A. Alshrief,
Mohammed E. Hassan,
Zahraa Nassar,
Amr A. El-Ella,
Mostafa A. Abdel-Maksoud,
Mohammed A. Hussein
Publication year - 2022
Publication title -
asian journal of chemistry/asian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.145
H-Index - 34
eISSN - 0975-427X
pISSN - 0970-7077
DOI - 10.14233/ajchem.2022.23456
Subject(s) - chemistry , lung , pharmacology , a549 cell , glutathione , carcinoma , medicine , cell , biochemistry , enzyme
Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids. It’s hydrophobic properties andpoor solubility in water, polymeric micellar systems exhibited improved antitumor efficacy becauseof a better solubilization and targeting after local and/or systemic administration. The aim of thepresent 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 cytotoxicactivity against A549 lung carcinoma cell line. Also, the anticancer activity of CEG-AgNPs (70.25mg/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 inlung 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-2and Bcl-2 gene expression as compared to control group. Daily oral administration of CEG-AgNPs tomice 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 lungCAT, GPx and GSH level. In addition, the CEG-AgNPs could inhibit lung VEGF-C, COX-2 andBcl-2 gene expression as compared to BaP treated mice. The histological and MRI examination showedthat a significant normalization has been observed through in CEG-AgNPs treated mice. Thebiochemical, histological and MRI results showed that CEG-AgNPs have potent anticancer activityagainst BaP-induced lung carcinoma through modulating multiple cellular behaviours and signalingpathways leading to the suppression of adaptive immune responses.