Liquiritin Enhances Chemosensitivity to Doxorubicin in Breast Cancer by Promoting Ubiquitination-Mediated Degradation of MCL1.

Breast cancer (BC) represents a life-threatening malignant disease that profoundly endangers women's health, with chemoresistance restricting treatment efficacy. Liquiritin (LIQ) has shown great potential in cancer therapy, yet its effect on the chemosensitivity of BC cells remains unclear. BC cells were treated with different concentration gradients of Doxorubicin (DOX) and LIQ. Cell counting kit-8 (CCK-8) assay, colony formation assay, and flow cytometry were employed to determine cell proliferation, apoptosis, and cell cycle progression. Western blot was applied to examine the levels of apoptosis-related proteins. The cycloheximide chase assay and immunoprecipitation were conducted to examine the degradation and ubiquitination levels of Myeloid Cell Leukemia-1 (MCL1). Finally, a BC xenograft mouse model was constructed to confirm the role of LIQ in vivo. In vitro experiments demonstrated that LIQ enhanced the chemosensitivity of BC cells to DOX and synergistically promoted DOX-induced apoptosis and cell cycle arrest. Moreover, the interaction between LIQ and DOX promoted the ubiquitination-mediated degradation of MCL1. Overexpression of MCL1 eliminated the sensitizing effect of LIQ to DOX. Additionally, LIQ enhanced the chemosensitivity of DOX in BC xenograft mice. LIQ enhanced DOX chemosensitivity in BC cells and xenograft models by promoting ubiquitination-mediated degradation of MCL1.