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Schisandrin B Attenuates Colitis-Associated Colorectal Cancer through SIRT1 Linked SMURF2 Signaling
Zhichen Pu1,2,3, Weiwei Zhang4, Minhui Wang1
1Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P. R. China.
Abstract:
Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75-30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 in vitro and in vivo. SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both in vitro and in vivo models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.
Insights
Schisandrin B effectively inhibits colon cancer growth and metastasis by reducing tumor size and cell proliferation. This compound impacts SMURF2 and SIRT1 protein levels, offering potential as a novel therapeutic agent for colon cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Colon cancer poses a significant global health threat with limited therapeutic advancements over the past 30 years.
- Investigating novel compounds for colon cancer treatment is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the anti-cancer effects of schisandrin B on colon cancer cell growth and metastasis.
- To elucidate the underlying molecular mechanisms involving SMURF2 and SIRT1.
Main Methods:
- Utilized a mouse model of colon cancer (AOM+DSS) and the HCT116 cell line.
- Employed techniques including Transwell migration assays, ELISA, Western blot, immunoprecipitation, and immunofluorescence.
- Administered varying doses of schisandrin B to treatment groups.
Main Results:
- Schisandrin B significantly reduced tumor number and size in the mouse model.
- The compound inhibited colon cancer cell proliferation and metastasis in vitro and in vivo.
- Schisandrin B induced SMURF2 expression and suppressed SIRT1, with SMURF2 negatively correlated with SIRT1 in human colorectal cancer.
Conclusions:
- Schisandrin B exhibits potent anti-cancer properties against colon cancer by modulating the SIRT1/SMURF2 pathway.
- The findings suggest schisandrin B as a promising lead compound for developing new colon cancer therapies.
- Targeting the SIRT1-SMURF2 interaction presents a potential therapeutic strategy for colon cancer treatment.
