PEG-4000 formed polymeric nanoparticles loaded with cetuximab downregulate p21 & stathmin-1 gene expression in cancer cell lines

Abdellatif, Ahmed A. H. and Tolba, Nahla Sameh and Alsharidah, Mansour and Al Rugaie, Osamah and Bouazzaoui, Abdellatif and Saleem, Imran and Maswadeh, Hamzah and Ali, Asmaa T. (2022) PEG-4000 formed polymeric nanoparticles loaded with cetuximab downregulate p21 & stathmin-1 gene expression in cancer cell lines. LIFE SCIENCES, 295: 120403. ISSN 0024-3205, 1879-0631

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Abstract

Cetuximab (CTX) is known to have cytotoxic effects on several human cancer cells in vitro; however, as CTX is poorly water soluble, there is a need for improved formulations can reach cancer cells at high concentrations with low side effects. We developed (PEG-4000) polymeric nanoparticles (PEGNPs) loaded with CTX and evaluated their in vitro cytotoxicity and anticancer properties against human lung (A549) and breast (MCF-7) cancer cells. CTX-PEGNPs were formulated using the solvent evaporation technique, and their morphological properties were evaluated. Further, the effects of CTX-PEGNPs on cell viability using the MTT assay and perform gene expression analysis, DNA fragmentation measurements, and the comet assay. CTX-PEGNP showed uniformly dispersed NPs of nano-size range (253.7 +/- 0.3 nm), and low polydispersity index (0.16) indicating the stability and uniformity of NPs. Further, the zeta potential of the preparations was -17.0 +/- 1.8 mv. DSC and FTIR confirmed the entrapping of CTX in NPs. The results showed IC50 values of 2.26 mu g/mL and 1.83 mu g/mL for free CTX and CTX-PEGNPs on the A549 cancer cell line, respectively. Moreover, CTX-PEGNPs had a lower IC50 of 1.12 mu g/mL in MCF-7 cells than that of free CTX (2.28 mu g/mL). The expression levels of p21 and stathmin-1 were significantly decreased in both cell lines treated with CTX-PEGNPs compared to CTX alone. The CTX-PEGNP-treated cells also showed increased DNA fragmentation rates in both cancer cell lines compared with CTX alone. The results indicated that CTX-PEGNP was an improved formulation than CTX alone to induce apoptosis and DNA damage and inhibit cell proliferation through the downregulation of P21 and stathmin-1 expression.

Item Type: Article
Uncontrolled Keywords: GOLD NANOPARTICLES; COLORECTAL-CANCER; DRUG-RELEASE; COMET ASSAY; DNA-DAMAGE; SIZE; SOLUBILITY; OVEREXPRESSION; PROLIFERATION; METASTASIS; Cetuximab; Polymeric nanoparticles; A549 lung cancer cell line; MCF-7 breast cancer cell line; Stathmin-1; Gene expression and regulation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Jan 2024 06:27
Last Modified: 30 Jan 2024 06:27
URI: https://pred.uni-regensburg.de/id/eprint/58466

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