Alloisoimperatorin enhances chemosensitivity by modulating the c-Myc-NBS1 axis to induce sustained DNA damage

Chemoresistance is a significant factor in the failure of cancer treatment. Although some chemotherapeutic combination regimens are linked to DNA damage repair processes, the therapeutic potential of TCM-derived small molecules that target these mechanisms is still underexplored. Alloisoimperatorin (Alloi) has demonstrated the ability to inhibit tumor growth; however, the efficacy and molecular mechanisms of itscombination with chemotherapeutic agents are not yet fully understood.Our findings demonstrate that Alloi enhances tumor sensitivity to GEM therapy by modulating the c-Myc-NBS1 axis. This modulation induces DNA damage and subsequently inhibits the DNA damage response (DDR) pathway. Thus, our resultssuggest a promising combinatorial therapeutic strategy for cancer treatment.