Green-Synthesized Silver Nanoparticles From Peel Extract of Pumpkin as a Potent Radiosensitizer Against Triple-Negative Breast Cancer (tnbc)

Abstract

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Radiation therapy (RT) is a modality for TNBC management. Radiosensitizers can mitigate the adverse effects of RT. Applying green-synthesized silver nanoparticles (Ag-NPs) from biological sources such as plants is a potential strategy to sensitize cancer cells to radiotherapy due to the low toxicity. Therefore, identifying novel natural sources for synthesizing stable and broadly applicable green-Ag-NPs has gained more attention in cancer therapy. In the present study, we synthesized green- Ag-NPs from pumpkin peel extract and elucidated the impact of green-synthesized Ag-NPs as a radiosensitizer in MDA-MB 231 cells (a model of TNBC). Results: The prepared Ag-NPs had a spherical shape with an average size of 81 nm and a zeta potential of - 9.96 mV. Combination of green-synthesized Ag-NPs with RT exhibited synergistic anticancer effects with an optimum combination index (CI) of 0.49 in MDA-MB-231 cells. Green-synthesized Ag-NPs synergistically potentiated RT-induced apoptosis in MDA-MB-231 cells compared to the corresponding monotherapies. Morphological features of apoptosis were further confirmed by the DAPI-TUNEL staining assay. HIF-1 alpha expression was decreased in cells subjected to combination therapy. Bax and p53 expression increased, whereas Bcl-2 genes decreased. Combination therapy significantly increased the protein level of PERK and CHOP while decreasing cyclin D1 and p-ERK/total ERK levels compared to monotherapies. Conclusion: These findings indicate the potential effect of green-synthesized Ag-NPs as a radiosensitizer for TNBC treatment.