Dietary Compound Diosmetin Chemosensitizes Breast Cancer Stem Cells by Suppressing HMGB1-mediated Autophagy

Integrative Medicine Research Center, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China

^* Corresponding author: ellen0000@126.com

Abstract

Breast cancer stem cells (CSCs) are a small cluster of highly tumorigenic cell subsets with self-renewal and multi-directional differentiation potential. Accumulating studies have shown that CSCs lead to chemotherapy resistance and recurrence of breast cancer, which is the main reason for the failure of chemotherapy in breast cancer. Autophagy is one of the key mechanisms to protect tumor cells from chemotherapeutic stimulation and other stresses, which contributes to the ultimate survival of CSCs in refractory or recurrent tumors. This study was carried out in terms of multiple strategies such as flow cytometry, stem-like detection, zebrafish tumor xenograft model construction, autophagy lentivirus construction, and western blotting analysis to prove that a natural flavonoid compound diosmetin safely and effectively promoted the tumor-killing effect of chemotherapeutic drug for breast cancer. The involved mechanism was closely related to its ability to reduce HMGB1 expression and subsequently block the autophagy pathway of breast CSCs. This study will provide new ideas and tools for the development of breast cancer drug resistance mechanism and targeted drugs.