Anti-Metastatic Effects of Plukenetia volubilis (Sacha Inchi) Husk Extract via EGFR and EMT Pathways and Other Antitumor Effects in Colon Cancer

Colorectal cancer treatment primarily relies on chemotherapy, which often causes significant side effects. Sacha inchi, a plant known in traditional medicine, has shown promise in various therapeutic applications. However, despite its potential, the specific mechanisms remain poorly understood, particularly regarding its husk components. This study investigates sacha inchi husk extract's chemical properties and its effects on human colorectal cancer cells. GC/MS and LC/MS analyses revealed a rich profile of phenolic and flavonoid compounds, with naringenin and lidocaine as predominant components. The extract demonstrated significant dose-dependent inhibition of colorectal cell migration, invasion, and colony formation while exhibiting no cytotoxicity toward normal colon epithelial cells. Transcriptomic and proteomic analyses showed downregulation of migration- and invasion-related genes in cancer cells, and Western blot analysis confirmed reduced expression of MMP2, MMP9, and N-cadherin. EGFR pathway analysis showed decreased expression of RAS (-0.2-fold), MAK (-0.26-fold), and ERK (-0.54-fold) genes, indicating suppression of epithelial-mesenchymal transition (EMT). These findings demonstrate that sacha inchi husk extract effectively inhibits metastasis in colorectal cancer cells through the upstream (EGFR) and downstream (EMT) pathways, suggesting its potential as a dietary supplement or therapeutic agent for colorectal cancer treatment. Our research provides evidence for the development of natural, less toxic alternatives.