The Publication:

Panaxynol alleviates colorectal cancer in a murine model via suppressing macrophages and inflammation

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Publication Summary:

Currently available therapies for colorectal cancer (CRC) have limited efficacy and severe adverse effects that may be overcome with the use of natural compounds as alternatives. We previously reported that panaxynol (PA), a bioactive component in American ginseng, possesses anticancer properties in vitro and suppresses murine colitis through its proapoptotic and anti-inflammatory properties. Because colitis is a predisposing factor of CRC and inflammation is a major driver of CRC, we sought to evaluate the therapeutic potential of PA in CRC. Mice were treated with azoxymethane-dextran sodium sulfate (AOM/DSS) to induce CRC. They were also treated with PA (2.5 mg/kg) or vehicle three times per week via oral gavage for 12 weeks. Our results showed that PA improved clinical symptoms and reduced tumorigenesis. This improvement may be reflective of PA's restorative effect on intestinal barrier function; PA upregulated the expression of essential tight junction and mucin genes and increased the abundance of mucin-producing goblet cells. Given that macrophages play a substantial role in the pathogenesis of CRC and that we previously demonstrated that PA targets macrophages in colitis, we next assessed macrophages. The data showed that PA reduces the relative abundance of colonic macrophages within the lamina propria, and this was consistent with a reduction in the expression of important markers of macrophages and inflammation. We further confirmed PA's inhibitory effects on macrophages in vitro under CRC conditions. These results suggest that PA is a promising agent to prevent or treat CRC given its ability to inhibit macrophages and modulate the inflammatory environment in the colon.