Feruloylated Arabinoxylan From Maize Bran Induces Cell Death in HCT 116 Colon Cancer Cells By the Cross-Talk of Apoptosis, Cell Survival, and Autophagy Pathways
摘要
Feruloylated arabinoxylan (F-AX), a hemicellulosic polysaccharide abundant in cereal brans, is gaining attention for its antioxidant, immunomodulatory, and anticancer properties. Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, and diet-derived bioactives offer promising complementary strategies for its prevention and management. In this study, F-AX was extracted from maize bran using a green chemistry approach and characterized as a highly branched arabinoxylan (AX) with a β-(1→4)-linked xylose backbone substituted with feruloylated arabinose residues. F-AX demonstrated significant antiproliferative activity against HCT 116 colon cancer cells in a dose- and time-dependent manner, with the highest inhibition of 84.68 ± 3.6% (p < 0.0001) observed at 3 mg/mL after 48 h treatment. Mechanistic investigations revealed induction of apoptosis, evidenced by increased caspase-3/7 activity, elevated cleaved PARP and cytochrome c levels, reduced procaspase-3, -8, and − 9 expression, decreased Bid and Bcl-xL levels, and loss of mitochondrial membrane potential. Autophagy induction was confirmed by increased LC3B-II/I ratio, increased expression of Beclin-1 and LAMP-1, and reduced p53 levels. F-AX activated the antioxidant pathway, reduced the ROS levels, decreased the p-Akt/Akt ratio and NF-κB levels while increasing PTEN expression, suggesting suppression of the PI3K/Akt/mTOR signaling pathway. These findings highlight cross-talk among apoptosis, autophagy, and PI3K/Akt/mTOR signaling in F-AX-induced cell death. In addition, F-AX exhibited resistance to simulated gastrointestinal digestion, suggesting its potential to reach the colon intact and exert localized colonic effects. Overall, this study highlights the potential of maize bran-derived F-AX as a nutraceutical candidate for CRC management and provides a foundation for further in vivo investigations.
Graphical Abstract