Panaxynol Alleviates Colorectal Cancer in a Murine Model via Suppressing Macrophages and Inflammation.

Abstract

Currently available colorectal cancer (CRC) therapies have limited efficacy and severe adverse effects that may be overcome with the alternative use of natural compounds. We previously reported that panaxynol (PA), a bioactive component in American Ginseng, possesses anti-cancer properties in vitro and suppresses murine colitis through its pro-apoptotic 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. AOM/DSS mice (C57BL/6) were administered 2.5mg/kg PA or vehicle 3x/week via oral gavage over 12 weeks. PA improved clinical symptoms (p≤0.05) and reduced tumorigenesis (p≤0.05). 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 (p≤0.05) and increased abundance of mucin-producing goblet cells (p≤0.05). 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. We show that PA reduces the relative abundance of colonic macrophages within the lamina propria (p≤0.05), and this was consistent with a reduction in the expression of important markers of macrophages and inflammation (p≤0.05). We further confirmed PA's inhibitory effects on macrophages in vitro under CRC conditions (p≤0.05). These results suggest that PA is a promising therapeutic compound to treat CRC and improve clinical symptoms given its ability to inhibit macrophages and modulate the inflammatory environment in the colon.