Green-synthesized silver nanoparticles from peel extract of pumpkin as a potent radiosensitizer against triple-negative breast cancer (TNBC)

• Published in: Cancer nanotechnology Vol. 15; no. 1; pp. 47 - 27
• Main Authors: Montazersaheb, Soheila, Eftekhari, Aziz, Shafaroodi, Amir, Tavakoli, Soodeh, Jafari, Sara, Baran, Ayşe, Baran, Mehmet Fırat, Jafari, Sevda, Ahmadian, Elham
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.12.2024; Springer Nature B.V; BMC
• Subjects: Anticancer; Apoptosis; Biochemistry; Biomedical Engineering and Bioengineering; Breast cancer; Cancer Research; Cancer therapies; Chemistry and Materials Science; Combination therapy; Gene expression; Green-synthesized Ag-NPs; Materials Science; Nanoparticles; Nanotechnology; Pumpkin; Pumpkins; Radiation; Radiation therapy; Radiosensitizers; Silver; Synergism; Synthesis; TNBC; Zeta potential; Green-synthesized Ag-NPs; TNBC; Anticancer; Synergism; Pumpkin; Radiation
• ISSN: 1868-6958; 1868-6966
• DOI: 10.1186/s12645-024-00285-z

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-1α 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. Graphical Abstract