Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis via the CHOP signalling pathway

Co, V. A.; El-Nezami, H.; Liu, Y.; Twum, B.; Dey, P.; Cox, P. A.; Joseph, S.; Agbodjan, R.; Sabzichi, M.; Draheim, R.; Wan, M. L. Y.

doi:10.1101/2023.08.27.554980

bioRxiv · 10.1101/2023.08.27.554980

Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis via the CHOP signalling pathway

Co, V. A.·El-Nezami, H.·Liu, Y.·Twum, B.·Dey, P.·Cox, P. A.·Joseph, S.·Agbodjan, R.·Sabzichi, M.·Draheim, R.·Wan, M. L. Y.

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Abstract

Colon cancer is among the most lethal and prevalent malignant tumours 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 Schisandra chinensis, has been reported for its anti-cancer properties. However, no studies to date have been done to characterise the exact molecular mechanisms regarding the anti-tumorigenic effect of Sch B in colon cancer. A comprehensive analysis of the molecular mechanism for the anti-tumorigenic effect of Sch B on human colon cancer cells was performed using 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, 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 tumour growth in vivo. Our findings provide essential background for clinical trials examining the effects of Sch B in patients with colon cancer.

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Co, V. A., El-Nezami, H., Liu, Y., Twum, B., Dey, P., Cox, P. A., Joseph, S., Agbodjan, R., Sabzichi, M., Draheim, R., Wan, M. L. Y.. 2023-08-27. Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis via the CHOP signalling pathway. https://doi.org/10.1101/2023.08.27.554980

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