Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Emerging evidence suggests a rising incidence of CRC in younger adults, emphasizing the urgent need for innovative therapeutic strategies. The increasing attention on circular economy approaches has heightened interest in discovering natural compounds derived from recycled agri-food waste. These compounds are particularly promising due to their large array of bioactive functional components. In this study, we investigated the efficacy of a green compost derived from coffee wastes, known as humic substance (HS), in reducing CRC cell viability. Chemical characterization of HS from composted coffee waste (HS-COF) using (13)C Cross-Polarization Magic-Angle Spinning Nuclear Magnetic Resonance (CPMAS NMR) spectroscopy and offline pyrolysis Tetramethylammonium Hydroxide-Gas Cromatography Mass-Spectrometry (TMAH-GC-MS) revealed an abundance of phenolic compounds derived from lignin residues. Specifically, chlorogenic acid (ClA) was identified as the major component and primary agent responsible for the biological effects of HS-COF. Our in vitro results demonstrated that HS-COF selectively inhibits HT-29 cell viability, migration, and proliferation by inducing programed cell death through the activation of the tumor necrosis factor-α (TNF-α) signaling pathway and disruption of calcium homeostasis. Additionally, HS-COF exhibited a significant antioxidant activity, indicating its potential to combine a cytotoxic profile with a safety profile, thereby minimizing adverse effects on healthy cells. In conclusion, this study proposes HS-COF as a valuable adjuvant in CRC therapy, paving the way for its application in the pharmaceutical industry.