Senolytics (DQ) Mitigates Radiation Ulcers by Removing Senescent Cells

Area of Science:

• Oncology
• Cell Biology
• Radiotherapy Research

Background:

• Radiation ulcers are a frequent and debilitating side effect of radiotherapy with no effective treatments.
• Accumulation of senescent cells post-radiation contributes to tissue dysfunction and ulcer development.

Purpose of the Study:

• To investigate the role of cellular senescence in the pathogenesis of radiation ulcers.
• To evaluate the therapeutic potential of senescent cell clearance in mitigating radiation ulcers.

Main Methods:

• Assessed p16 expression as a senescence biomarker in human radiation ulcers and animal models.
• Investigated the senescence-associated secretory phenotype (SASP) and its effects.
• Administered a senolytics cocktail (Dasatinib plus Quercetin - DQ) to senescent cell-burdened animal models.
• Examined the impact of DQ on tumor cell apoptosis and radiosensitivity in CAL-27 and MCF-7 cell lines.

Main Results:

• Increased p16 expression confirmed cellular senescence in human radiation ulcers and induced persistent senescence in animal models.
• Senescent cells secreted SASP, promoting senescence in adjacent cells, an effect reduced by JAK inhibition.
• Treatment with DQ significantly mitigated radiation ulcers in animal models.
• DQ treatment induced tumor cell apoptosis and enhanced radiosensitivity in tested cell lines.

Conclusions:

• Cellular senescence plays a critical role in the development of radiation ulcers.
• Targeting and eliminating senescent cells represents a promising therapeutic strategy for managing radiation ulcers and improving radiotherapy outcomes.