Cirsiliol regulates mitophagy in colon cancer cells via STAT3 signaling

作者：Tao Jiang, Lulu Peng, Qian Wang, Bingyu Huang, Dewei Peng, Lintong Men, Yue Jiang, Mengying Zhu, Moran Wang, Li Lin, Jiagao Lv, Sheng Li · 发表于：Cancer Cell International · 年份：2022 · DOI：10.1186/s12935-022-02732-6 · 被引用次数：42 · 研究领域：Autophagy in Disease and Therapy、Cell death mechanisms and regulation、Cytokine Signaling Pathways and Interactions

BACKGROUND: Mitophagy is a type of selective autophagy for dysfunctional mitochondria and plays a key role in tumorigenesis and cancer progression. However, whether mitophagy plays a role in colon cancer remains unclear. Cirsiliol is a natural product and has been found to exert anti-cancer effects in multiple tumors. The effects of cirsiliol in the tumorigenesis and progression of colon cancer remain unknown. METHODS: CCK8 assay, plate cloning assay, and cell scratch assay were performed to determine cell viability, colony formation, and wound healing abilities of HCT116 and SW480 cells. JC-1 staining, H2DCFDA staining, and Mito-Tracker Red staining were carried out to evaluate mitochondrial membrane potential (Δψm), intracellular reactive oxygen species (ROS) level, and mitochondrial morphology. Molecular docking technology was utilized to predict interaction of cirsiliol and signal transducer and activator of transcription 3 (STAT3). Immunofluorescence staining was used to measure nuclear translocation of STAT3. The protein levels of phosphorylated STAT3 (Y705), total STAT3, and mitophagy proteins were detected by western blot. RESULTS: In this study, we first found that cirsiliol inhibited cell viability, colony formation, and wound healing abilities of HCT116 and SW480 colon cancer cells. Moreover, cirsiliol suppressed Δψm, increased ROS production, and disrupted mitochondrial morphology via inhibiting the levels of mitophagy proteins including PINK1, Parkin, BNIP3, and ...