
Animal Models and Experimental Medicine, Journal Year: 2024, Volume and Issue: 7(5), P. 591 - 605
Published: Aug. 13, 2024
Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and potential therapeutic applications for the condition. Fisetin, natural flavonoid found in various fruits vegetables, has shown promise managing CRC due its diverse biological activities. It influence key cell signaling pathways related inflammation, angiogenesis, apoptosis, transcription factors. The results this study demonstrate that fisetin induces colon apoptosis through multiple mechanisms. impacts p53 pathway, leading increased levels decreased murine double minute 2, contributing induction. Fisetin also triggers release important components apoptotic process, such as second mitochondria-derived activator caspase/direct inhibitor apoptosis-binding protein with low pI cytochrome c. Furthermore, inhibits cyclooxygenase-2 wingless-related integration site (Wnt)/epidermal growth factor receptor/nuclear kappa B pathways, reducing Wnt target gene expression hindering colony formation. achieves by regulating activities cyclin-dependent kinase 2 4, retinoblastoma phosphorylation, decreasing cyclin E levels, increasing p21 ultimately influencing E2 promoter binding 1 division cycle (CDC2) levels. Additionally, exhibits effects on cells, inhibiting phosphorylation Y-box ribosomal S6 kinase, promoting extracellular signal-regulated 1/2, disrupting repair process DNA double-strand breaks. Moreover, serves an adjunct therapy prevention treatment phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA)-mutant CRC, resulting reduction phosphatidylinositol-3 (PI3K) expression, Ak strain transforming mTOR activity, downstream proteins cells PIK3CA mutation. These findings highlight multifaceted position it promising candidate future development.
Language: Английский