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
Full text not available from this repository. (Request a copy)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 |
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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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