Dietary Natural Flavonoid Kaempferitrin Treats Colorectal Cancer by Targeting on the PI3K/AKT Signaling Pathway

Abstract

Colorectal cancer is the third most prevalent cancer of all cancer types worldwide, with an expected 2.4 lakhs incidences by 2035. Flavonoids are a wide variety of polyphenols generally found to have proven nutritional benefits. Kaempferitrin (Kaempferol-3,7-di-O-alpha-L-rhamnoside) is a glycosyloxyflavone which is kaempferol coupled to \(\alpha\)-rhamnopyranosyl residues between positions 3 and 7 respectively via glycosidic linkages. The molecular formula C27H30O14 and has a molecular weight of kaempferitrin 578.52 g/mol. Kaempferitrin a natural flavonoid has been extracted from many edible plants that have reported anti-oxidant, anti-inflammatory, anti-diabetic, anti-convulsant activities. Apoptosis induction, ROS production, and colorectal cancer (HT-29) cell viability can all be inhibited by kaempferitrin in a concentration-dependent manner. Additionally activating caspase-3 and increasing the ratios of cleaved PARP protein expression in HT-29 cells, kaempferitrin induced caspase-dependent apoptosis. These kaempferitrin mediated apoptosis also exhibit a positive correlation with the PI3/AKT pathway, suggesting that the HT-29 cancer cells may be targeted downstream. Recent research has linked the PI3K/AKT pathway to the development of tumors and controls cell death, differentiation, and proliferation. Many malignancies, including colorectal cancer, had a significant activation of the protein kinase B (PI3K/AKT) signaling pathway. Inhibiting the PI3K/AKT pathways also results in mitochondrial dysfunction, which produces ROS and kills cancer cells.