Synergistic effect of chrysin and radiotherapy against triple-negative breast cancer (TNBC) cell lines
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Sevda Jafari [1] ; Sheida Dabiri [1] ; Elnaz Mehdizadeh Aghdam [1] ; Ezzatollah Fathi [2] ; Nazli Saeedi [1] ; Soheila Montazersaheb [1] ; Raheleh Farahzadi [1]
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[1] Tabriz University of Medical Sciences
Tabriz University of Medical Sciences
Irán
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[2] University of Tabriz
University of Tabriz
Irán
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- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 8 (August), 2023, págs. 2559-2568
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
Purpose Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer, accounting for 20% of cases. Due to the lack of a molecular target, limited options are available for TNBC treatment. Radiation therapy (RT) is a treatment modality for the management of TNBC following surgery; however, it has a detrimental effect on surrounding healthy tissues/cells at a higher rate.
Methods We examined the effect of RT in combination with chrysin as a possible radiosensitizing agent in an MDA-MB-231 cell line as a model of a TNBC. The growth inhibitory effects of chrysin were examined using an MTT assay. Flow cytometry was performed to evaluate apoptosis and expression of hypoxia-induced factor-1α (HIF-1α). The protein expression of p-STAT3/STAT3 and Cyclin D1 was examined using western blotting. Real-time PCR determined apoptotic-related genes (Bax, BCL2, p53).
Results Treatment of MDA-MB-231 cells with chrysin in combination with RT caused synergistic antitumor effects, with an optimum combination index (CI) of 0.495. Our results indicated that chrysin synergistically potentiated RT-induced apoptosis in MDA-MB-231 compared with monotherapies (chrysin and/or RT alone). Expression of HIF-1α was decreased in the cells exposed to combinational therapy. The apoptotic effect of combinational therapy was correlated with increased Bax (pro-apoptotic gene) and p53 levels along with reduced expression of Bcl-2 (anti-apoptotic gene). Increased apoptosis was associated with reduced expression of Cyclin D1, p-STAT3.
Conclusion These findings highlight the potential effect of chrysin as a radiosensitizer, indicating the synergistic anti-cancer effect of chrysin and RT in TNBC. Further investigation is warranted in this regard.
