Abstract
Background
Oral tongue squamous cell carcinoma (OTSCC) is a popular aggressive malignancy of the oral cavity. Despite advances in OTSCC therapy, the overall 5-year survival rate is low. The tumor microenvironment resistance factors lead to chemotherapy failure, especially intratumoral hypoxia. HIF-1α, the main protein in hypoxia pathway, influences cell survival and angiogenesis. Hypoxia/HIF-1α system is a potential strategic target in cancer therapeutics. The expression of hypoxia-regulating miRNAs (hypoxamiRs; miR-210 and miR-21), regulators of HIF-1α, is high in OTSCC. Gum Arabic-encapsulated gold nanoparticles (GA-AuNPs) have been reported as promising modality in cancer treatment.
Objective
This study aimed to investigate the influence of GA-AuNPs on the hypoxia regulators in OTSCC (CAL-127 cells). GA-AuNPs cytotoxicity assessed by MTT assay; cell death mode was detected by dual DNA staining; monitoring of cellular hypoxia was followed by pimonidazole; miR-210 and miR-21 expression was assessed by qPCR; and their targets (HIF-1α and c-Myc) assayed by immunocytofluorescence and ELISA, respectively.
Results
GA-AuNPs (75–80 nm; λmax of ~ 540 nm) reduced cell viability with IC50 of 392.3 and 247.3 µg/ml after 24 h and 48 h, respectively. Cell death was mainly due to apoptosis. CAL-27 cells exhibited high hypoxia and the treatment with GA-AuNPs inhibited this hypoxia in a dose-dependent manner, as detected by pimonidazole. GA-AuNPs (30% IC50) significantly reduced miR-210 and miR-21 expression. HIF-1α and c-Myc were inhibited by GA-AuNPs (30% IC50, for 48 h).
Conclusion
The study findings may suggest GA-AuNPs as a promising carrier for chemotherapies to diminish intratumoral hypoxia-stimulated resistance.
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This work was supported by Taif University Researchers Supporting Project Number (TURSP-2020/103).
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AMG-E designed the study, carried out the molecular biology experiments, and wrote the manuscript; HMB reviewed the manuscript; NSA reviewed the manuscript; EMI contributed in the cell biology part; WFA carried out the fluorescence microscopy analysis; FA contributed in cell biology part and statistics; and BMR contributed in nanoparticles preparation and characterization.
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Gamal-Eldeen, A.M., Baghdadi, H.M., Afifi, N.S. et al. Gum arabic-encapsulated gold nanoparticles modulate hypoxamiRs expression in tongue squamous cell carcinoma. Mol. Cell. Toxicol. 17, 111–121 (2021). https://doi.org/10.1007/s13273-021-00117-w
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DOI: https://doi.org/10.1007/s13273-021-00117-w