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

Ahmed A. Emara1, Ahmed M. Darwesh1, Mohamed A. Mostafa1, Ahmed A. Ahmed1, Khaled W. Rashad1, Abdullah M. Said1, Abdelrahman E. Elsebaay1, Khaled M. Nasser1, Abdelrehem S. Amin1, Mohamed S. Gamil1, Foad H. Mohamed1, Mohamed K. Ahmed1, Diana A. Alshrief1, Mohammed E. Hassan2, Zahraa Nassar2, Amr A. El-Ella3, Mostafa A. Abdel-Maksoud4 and Mohammed A. Hussein5,*,

1Department of Radiology and Medical Imaging, Faculty of Applied Medical Science, October 6th University, October 6th City, Egypt

2Department of Medical Laboratories, Faculty of Applied Medical Sciences, October 6 University, Sixth of October City, Egypt

3Department of Measurements, Photochemistry and Agriculture Applications. National Institute of Laser Enhanced Science, Cairo University, Giza, Egypt

4Department of Radiology and Medical Imaging, Faculty of Medicine, Sudan University of Sciences and Technology, Khartoum, Sudan

5Department of Biochemistry, Faculty of Applied Medical Science, October 6th University, October 6th City, Egypt

*Corresponding author: Tel: +20 124832580; E-mail: prof.husseinma@o6u.edu.eg

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.

Keywords

Cucurbitacin-E-glucoside, BaP, Lung carcinoma, Gene expression, Antioxidant enzyme, Cytokine storm.

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