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Published on: July 17, 2018
Cirsiliol regulates mitophagy in colon cancer cells via STAT3 signaling
Tao Jiang1,2, Lulu Peng2, Qian Wang2
1Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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 FUNDC1. Application of mitophagy activator improved the levels of mitophagy-related proteins, and ameliorated Δψm and ROS levels. According to the result of molecular docking, we found that cirsiliol potentially bound to the SH2 domain of STAT3, the key domain for the functional activation of STAT3. Moreover, it was found that cirsiliol inhibited constitutive and IL‑6‑induced STAT3 phosphorylation and nuclear translocation by western blot and immunofluorescence analysis. Comparing with cirsiliol group, we found that overexpression of STAT3 restored the expressions of mitophagy proteins.
Conclusions:
Cirsiliol targets STAT3 to inhibit colon cancer cell proliferation by regulating mitophagy.
Insights
Cirsiliol, a natural compound, inhibits colon cancer cell growth by targeting STAT3 and regulating mitophagy, a process crucial for mitochondrial health and cancer progression.
Area of Science:
- Cell Biology
- Cancer Research
- Mitochondrial Dynamics
Background:
- Mitophagy, the selective degradation of damaged mitochondria, is implicated in cancer development and progression.
- The role of mitophagy in colon cancer and the effects of the natural compound cirsiliol remain largely unexplored.
- Cirsiliol has demonstrated anti-cancer properties in various tumor types.
Purpose of the Study:
- To investigate the role of mitophagy in colon cancer.
- To determine the effects of cirsiliol on colon cancer cell proliferation and mitophagy.
- To elucidate the molecular mechanism by which cirsiliol exerts its anti-cancer effects in colon cancer.
Main Methods:
- Cell viability, colony formation, and wound healing assays were used to assess colon cancer cell behavior.
- Mitochondrial function was evaluated using JC-1, H2DCFDA, and Mito-Tracker Red staining.
- Molecular docking, western blotting, and immunofluorescence were employed to analyze STAT3 signaling and mitophagy-related protein levels.
Main Results:
- Cirsiliol significantly inhibited colon cancer cell viability, proliferation, and migration.
- Cirsiliol disrupted mitochondrial membrane potential, increased reactive oxygen species (ROS) production, and altered mitochondrial morphology by inhibiting mitophagy proteins (PINK1, Parkin, BNIP3, FUNDC1).
- Cirsiliol targeted STAT3, inhibiting its phosphorylation and nuclear translocation, thereby restoring mitophagy protein expression.
Conclusions:
- Cirsiliol effectively inhibits colon cancer cell proliferation.
- The anti-cancer effects of cirsiliol are mediated through the STAT3 signaling pathway and regulation of mitophagy.
- Cirsiliol represents a potential therapeutic agent for colon cancer treatment.
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