Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles

Abstract

Purpose This study was conducted to verify the induction and mechanism of selective apoptosis in G361 melanoma cells using anti-HER2 antibody-conjugated gold nanoparticles (GNP-HER2). Materials and Methods Following GNP-HER2 treatment of G361 cells, cell cycle arrest and apoptosis were measured by WST-1 assay, Hemacolor staining, Hoechst staining, immunofluorescence staining, fluorescence-activated cell sorting analysis, and Western blotting. Results G361 cells treated with GNP-HER2 showed condensation of nuclei, which is an apoptotic phenomenon, and translocation of apoptosis-inducing factor and cytochrome c from mitochondria into the nucleus and cytoplasm, respectively. Increases in BAX in cells undergoing apoptosis, activation of caspase-3 and -9, and fragmentation of poly (ADP-ribose) polymerase and DNA fragmentation factor 45 (inhibitor of caspase-activated DNase) were observed upon GNP-HER2 treatment. Following GNP-HER2 treatment, an increase of cells in sub-G1 phase, which is a signal of cell apoptosis, was observed. This resulted in the down-regulation of cyclin A, cyclin D1, cyclin E, cdk2, cdk4, and cdc2 and the up-regulation of p21. Thus, GNP-HER2 treatment was confirmed to induce the cessation of cell cycle progression. Also, decreases in phospho-focal adhesion kinase and phospho-human epidermal growth factor receptor, which activate cellular focal adhesion, and decreases in phospho-paxillin, which stimulates the disassembly of filamentous actin, were observed. Reduced cell adhesion and disassembly of the intracellular structure indicated cell deactivation. Conclusion GNP-HER2 can selectively kill G361 melanoma cells without affecting normal cells. The mechanism of G361 cell death upon treatment with GNP-HER2 was apoptosis accompanied by activation of caspases.

Anticancer Efficacy of Nonthermal Plasma Therapy Combined with PD-L1 Antibody Conjugated Gold Nanoparticles on Oral Squamous Cell Carcinoma

“…In contrast, SCC-25 cells treated with PD-L1 ab + GNP showed strong red staining in the cytoplasm around the nucleus (Figure 3). Similar to a previous study [34], higher levels of antibody-GNP uptake were observed in the cancer cells. These results confirmed the selective binding of SCC-25 cells by the PD-L1 antibody + GNP.…”

Cardiac Melanoma Metastasis with ERBB2 Gene Amplification: A Potential for Future Targeted Therapy

“…It encodes the HER2 receptor, which is a tyrosine-kinase receptor and a tumor factor from a superfamily of EGFR markers that controls growth, survival, adhesion and migration of the cells. It follows an intracellular signal pathway that controls enhancement or suppression of the cell [15]. Mutations in the ERBB2 gene that carry a gene transcription for HER2 receptors, can lead to uncontrolled cell proliferation and oncogenesis.…”

Nanochemistry of gold: from surface engineering to dental healthcare applications

“…For instance, the expression of cluster of differentiation 24 (CD24) is closely intertwined with tumorigenesis and neoplastic diseases. 181 CD24-GNPs have proven to be promising and highly sensitive biomarkers in diagnosing salivary gland tumors and predicting prognosis. 182 Another example is in distinguishing between oral lesions, where GNR-EGFR monoclonal antibodies have been deployed to differentiate between benign and potentially malignant human oral lesions.…”

“…GNSs are reported for use in specific treatments for melanomas. 181,206 Melanoma cells overexpress focal adhesion kinase (FAK) compared with normal cells. Choi et al combined GNPs with antibodies targeting phosphorylated FAK, and found a selective killing effect on melanoma cells with non-thermal atmospheric pressure plasma by inducing apoptosis.…”