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Schisandrin B Suppresses Colon Cancer Growth by Inducing Cell Cycle Arrest and Apoptosis: Molecular Mechanism and
Vanessa Anna Co1, Hani El-Nezami1,2, Yawen Liu3
1School of Biological Sciences, Faculty of Science, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam Hong Kong.
Abstract:
Colon cancer is among the most lethal and prevalent malignant tumors in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruit ofSchisandra chinensis, has been reported for its anticancer properties. However, to date, no studies have been done to characterize the exact molecular mechanisms underlying the antitumorigenic effects of Sch B in colon cancer. This study aimed to explore the antitumorigenic effects of Sch B in colon cancer and to understand the underlying therapeutic mechanism. A comprehensive analysis of the molecular mechanism underlying the antitumorigenic effects of Sch B on human colon cancer cells was performed using a combination of Raman spectroscopy, RNA-seq, computational docking, and molecular biological experiments. The in vivo efficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines. Raman spectroscopy, computational, RNA-seq, and molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis. CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis. Sch B reduced colon tumor growth in vivo. Our findings demonstrated that Sch B induced apoptosis and inhibited cell proliferation and tumor growth in vitro and in vivo. These results provided an essential background for clinical trials examining the effects of Sch B in patients with colon cancer.
Insights
Schisandrin B (Sch B) effectively inhibits colon cancer growth by inducing apoptosis. This natural compound activates the unfolded protein response via CHOP, offering a promising therapeutic avenue for colon cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Colon cancer is a leading cause of cancer-related deaths globally.
- Existing therapies for colon cancer have limitations, necessitating novel treatment strategies.
- Schisandrin B (Sch B), derived from *Schisandra chinensis*, shows potential anticancer activity, but its mechanism in colon cancer is unclear.
Purpose of the Study:
- To investigate the antitumorigenic effects of Schisandrin B (Sch B) in colon cancer.
- To elucidate the molecular mechanisms underlying Sch B's therapeutic action.
- To evaluate Sch B's efficacy in preclinical colon cancer models.
Main Methods:
- Utilized Raman spectroscopy, RNA-sequencing (RNA-seq), computational docking, and molecular/cellular experiments.
- Assessed *in vitro* effects on human colon cancer cell lines.
- Evaluated *in vivo* efficacy using a mouse xenograft model.
Main Results:
- Sch B significantly reduced colon cancer cell proliferation and induced apoptosis.
- Sch B activated the unfolded protein response by upregulating and interacting with CHOP.
- CHOP knockdown diminished Sch B's effects on cell viability and apoptosis, confirming CHOP's role.
- Sch B inhibited colon tumor growth in a mouse xenograft model.
Conclusions:
- Schisandrin B demonstrates significant antitumorigenic effects against colon cancer both *in vitro* and *in vivo*.
- The mechanism involves Sch B-induced apoptosis mediated by the CHOP-dependent unfolded protein response.
- These findings support Sch B as a potential candidate for clinical trials in colon cancer patients.
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