Androsin alleviates colorectal cancer by inhibiting the PI3K/Akt-centered signaling pathway

Androsin is a phenolic acid compound extracted from <i>Picrorhiza kurroa</i> with apocynin as its aglycone. Early studies have shown that apocynin exhibits specific inhibition towards NADPH oxidases (NOXs) and has some therapeutic effects on colorectal cancer (CRC). However, the effects and mechanisms of androsin on CRC remain unexplored. Based on the network pharmacology analysis, this study investigates the mechanisms of androsin on CRC at molecular, cellular, and animal tissue levels. Results indicate that in the high-concentration range, androsin induces apoptosis and inhibits the proliferation of CRC cell in a concentration-dependent manner, with IC₅₀ values of 56 μM and 41 μM after 48 h and 72 h, respectively. Although androsin do not affect cell viability in the low-concentration range, they significantly inhibit cell invasion, migration, and reactive oxygen species (ROS) production. In animal models, androsin suppresses tumor growth in nude mice and disrupts tumor tissues, as shown by hematoxylin-eosin staining, immunohistochemical analysis of Ki-67, and TUNEL assays. Mechanistically, androsin promotes apoptosis <i>via</i> the PI3K/Akt/mTOR/caspase3/PARP pathway in the high-concentration range, and inhibits invasion and migration <i>via</i> the NOX2/ROS/FAK/PI3K/Akt/NF-κB/MMP7 pathway in the low-concentration range. These findings not only verified the prediction from network pharmacology, but also provided a preliminary basis for exploring androsin's anti-CRC mechanisms and its potential as a therapeutic molecule or lead compound.