Copyright (c) 2022 AJC
This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis of CEG-AgNPs as a Promising MMPs/COX-2/Bcl-2 Signaling Pathway Modulator in BaP-Induced Lung Carcinoma
Corresponding Author(s) : Mohammed A. Hussein
Asian Journal of Chemistry,
Vol. 34 No. 2 (2022): Vol 34 Issue 2
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.
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K.S. Lee and M.A. El-Sayed, J. Phys. Chem. B, 110, 19220 (2006); https://doi.org/10.1021/jp062536y
M.S. Abd El-Lat, D.A. Yousif, N.A. Ahmed, G.R. Abd Allah, Y.A. Elbagoury, N.E. El Sayed, H.A. Hassan, B.M. El-hefnawy, A.R. Nageh, E.-S.S. Amer, A.H. Mohamed, N.A. Gobba and M.A. Hussein, Pak. J. Nutr., 20, 37 (2021); https://doi.org/10.3923/pjn.2021.37.45
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M.A. Hussein, H.A. El-gizawy, N.A. Gobba and Y.O. Mosaad, Curr. Pharm. Biotechnol., 18, 677 (2017); https://doi.org/10.2174/1389201018666171004144615
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D. Majumder, R. Debnath and D. Maiti, Life Sci., 260, 118384 (2020); https://doi.org/10.1016/j.lfs.2020.118384
J. Briede, M. Stivriòa, D. Stoldere, E. Bisenieks, J. Uldriíis, J. Poikâns, N. Makarova and G. Duburs, Cell Biochem. Funct., 22, 219 (2004); https://doi.org/10.1002/cbf.1091
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M.M. Ghorab, Z.H. Ismail and M. Abdalla, Arzneimittel-Forschung/ Drug Res., 60, 87 (2010); https://doi.org/10.1055/s-0031-1296254
M.A. Hussein, J. Med. Food, 21, 246 (2013); https://doi.org/10.1089/jmf.2012.0183