Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells

Ting-Chun Lin; Anand Soorneedi; Yingxue Guan; Ying Tang; Eleanor Shi; Matthew D Moore; Zhenhua Liu

doi:10.3389/fphar.2023.1203087

Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells

Front Pharmacol. 2023 Aug 16:14:1203087. doi: 10.3389/fphar.2023.1203087. eCollection 2023.

Authors

Ting-Chun Lin¹, Anand Soorneedi², Yingxue Guan¹, Ying Tang¹, Eleanor Shi³, Matthew D Moore², Zhenhua Liu^{1

4}

Affiliations

¹ Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, United States.
² Department of Food Science, University of Massachusetts, Amherst, MA, United States.
³ Chobanian and Avedisian School of Medicine, Boston University, Boston, MA, United States.
⁴ UMass Cancer Center, University of Massachusetts Chan Medical School, Worcester, MA, United States.

Abstract

Introduction: Diet-induced obesity has been shown to decrease the abundance of Turicibacter, a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of Turicibacter potentially influential in the protection of intestinal tumorigenesis. Recently, Antrodia camphorata (AC), a medicinal fungus native to Taiwan, has emerged as a promising candidate for complementary and alternative cancer therapy. Small molecules and polysaccharides derived from AC have been reported to possess health-promoting effects, including anti-cancer properties. Methods: Bacterial culture followed with cell culture were used in this study to determine the role of Turicibacter in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with Turicibacter fermentation. Results: Turicibacter fermentation and the addition of AC polysaccharide led to a significant increase in the production of nutrients and metabolites, including α-ketoglutaric acid and lactic acid (p < 0.05). Treatment of Turicibacter fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including Tph1, Htr1d, Htr2a, Htr2b, and Htr2c (p < 0.05), and Wnt-signaling related protein and downstream gene expressions, such as phospho-GSK-3β, active β-catenin, c-Myc, Ccnd1, and Axin2 (p < 0.05). Additionally, it triggered the highest generation of reactive oxygen species (ROS), which activated PI3K/Akt and MAPK/Erk signaling and resulted in cleaved caspase-3 expression. In comparison, the treatment of AC polysaccharide without Turicibacter fermentation displayed a lesser effect. Discussion: Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and Wnt-signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by Turicibacter fermentation.

Keywords: Turicibacter; Wnt/βcatenin signaling; colorectal cancer; microbiome; mushroom polysaccharide; reactive oxygen species; serotonin.

Grants and funding

This work was supported in part by USDA/NIFA AFRI grants (2022-67018-36986, ZL), USDA/NIFA Hatch project (MAS00586, ZL) and Industrial funds. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the USDA or NIFA.