Chrysin potentiates the effects of Radiotherapy

The authors of this study investigated the potential of chrysin, a natural flavonoid, in enhancing radiation therapy (RT)-induced immunogenic cell death (ICD) in melanoma cells, specifically the B16-F10 cell line. The primary objective was to assess whether chrysin could potentiate the effects of RT, a standard cancer treatment but limited by its potential damage to surrounding healthy tissues. The study aimed to explore combination therapies to enhance the anti-cancer efficacy of RT while minimizing damage to normal cells.

Chrysin has demonstrated various anti-cancer properties, including the ability to induce apoptosis, inhibit cancer cell proliferation, and reduce the expression of pro-tumorigenic proteins such as STAT3 and PD-L1. This study builds on previous findings by examining chrysin's role in inducing ICD, a form of cell death that stimulates a specific anti-tumor immune response. ICD is characterized by releasing damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), ATP, HSP70, and HMGB1. These molecules play a crucial role in recruiting immune cells to the tumor site, thus triggering an immune response against the tumor.

The experimental design involved treating B16-F10 melanoma cells with different concentrations of chrysin, either alone or in combination with RT at doses of 2 Gy and 4 Gy. Cell viability assays, flow cytometry, and western blotting were used to evaluate the effects of these treatments on cell survival, apoptosis induction, and DAMP release. The combination of chrysin and RT showed a synergistic anti-cancer effect, as evidenced by increased apoptosis and higher levels of DAMPs compared to the effects of chrysin or RT alone.

One of the key findings was that chrysin significantly enhanced CRT surface exposure and the release of HSP70, HMGB1, and ATP when combined with RT. These results suggest that combination therapy is more effective at inducing ICD, thus potentially improving immune recognition of the tumor and promoting an anti-tumor immune response.

Furthermore, the study examined the impact of chrysin and RT on the expression of STAT3 and PD-L1, two proteins known to contribute to tumor immune evasion. Chrysin alone reduced the expression of p-STAT3 and PD-L1, and the combination with RT further amplified this effect. This indicates that chrysin not only enhances the efficacy of RT but also counters tumor-induced immunosuppression by downregulating key immune checkpoint proteins.

The study also investigated the effect of conditioned media from treated B16-F10 cells on dendritic cells (DCs), essential for initiating an immune response. The results showed that conditioned media from cells treated with chrysin and RT led to increased IL-12 secretion by DCs, indicating enhanced functional maturation of DCs and the potential for a stronger anti-tumor immune response.

This study highlights the potential of chrysin as a radiosensitizer that can enhance RT-induced ICD in melanoma cells. By increasing DAMP release and reducing immunosuppressive signals, chrysin may improve the immune system's ability to recognize and destroy tumor cells.

References

Jafari, S., Ardakan, A.K., Aghdam, E.M. et al. Induction of immunogenic cell death and enhancement of the radiation-induced immunogenicity by chrysin in melanoma cancer cells. Sci Rep 14, 23231 (2024). https://doi.org/10.1038/s41598-024-72697-1