Diosmetin as a dual-action modulator of cytoprotection and senescence in a breast cancer model

Abstract

This study evaluated the dual adjuvant potential of the flavonoid Diosmetin (DIOS) in breast cancer therapy using doxorubicin (DOX) or radiation (20 Gy). DIOS (80 µM) exhibited cytoprotective and genoprotective efficacy in non-tumorigenic MCF10-A cells by significantly reducing ROS levels and DNA damage (AP sites, $\gamma$H2AX foci), and enhancing antioxidant enzymes (SOD, CAT) and DNA repair genes (OGG1, ATM, ATR). Simultaneously, in MCF-7 cancer cells, DIOS acted as a senomorphic agent, significantly suppressing Therapy-Induced Senescence (TIS) and downregulating pro-oncogenic SASP mediators including IL-6 and HIF-1. These results demonstrate DIOS's capacity to both mitigate treatment toxicity in healthy tissues and limit tumor progression by normalizing the tumor microenvironment (TME).