AUTHOR=Lin Ting-Chun , Soorneedi Anand , Guan Yingxue , Tang Ying , Shi Eleanor , Moore Matthew D. , Liu Zhenhua 

TITLE=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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1203087

DOI=10.3389/fphar.2023.1203087

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Diet-induced obesity has been shown to decrease the abundance of <italic>Turicibacter</italic>, a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of <italic>Turicibacter</italic> potentially influential in the protection of intestinal tumorigenesis. Recently, <italic>Antrodia camphorata</italic> (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.</p><p><bold>Methods:</bold> Bacterial culture followed with cell culture were used in this study to determine the role of <italic>Turicibacter</italic> in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with <italic>Turicibacter</italic> fermentation.</p><p><bold>Results:</bold><italic>Turicibacter</italic> 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 (<italic>p</italic> &lt; 0.05). Treatment of <italic>Turicibacter</italic> fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including <italic>Tph1, Htr1d, Htr2a, Htr2b</italic>, and <italic>Htr2c</italic> (<italic>p</italic> &lt; 0.05), and <italic>Wnt</italic>-signaling related protein and downstream gene expressions, such as phospho-GSK-3β, active β-catenin, <italic>c-Myc, Ccnd1, and Axin2</italic> (<italic>p</italic> &lt; 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 <italic>Turicibacter</italic> fermentation displayed a lesser effect.</p><p><bold>Discussion:</bold> Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and <italic>Wnt</italic>-signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by <italic>Turicibacter</italic> fermentation.</p>