Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis: molecular mechanism and therapeutic potential

Vanessa Anna Co, Hani El-Nezami, Yawen Liu, Bonsra Twum, Priyanka Dey, Paul A. Cox, Shalu Joseph, Roland Agbodjan-Dossou, Mehdi Sabzichi, Roger Draheim, Murphy Lam Yim Wan

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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 of Schisandra 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.
Original languageEnglish
Pages (from-to)863-877
JournalACS Pharmacology & Translational Science
Volume7
Issue number3
Early online date22 Feb 2024
DOIs
Publication statusPublished - 8 Mar 2024

Keywords

  • apoptosis
  • cell cycle arrest
  • molecular docking
  • novel colon cancer treatment
  • Raman spectral change
  • schisandrin B

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