Anti-cancer Properties of Myricetin Against HT-29 Colon Cancer Cells Through Regulation of RIPK1/RIPK3 Signaling Pathway

Abstract

Background: Myricetin (MCN), a dietary flavonoid, is present in walnuts, fruits, vegetables, tea, and berries and has been suggested as an anti-inflammatory, antiplatelet, antimicrobial, antioxidant, and antiviral drug. Objectives: This study aimed to investigate whether the necroptosis pathway involves the toxic impacts of myricetin (MCN) on the colon adenoma-carcinoma HT-29 cells. Methods: For 48 hours, HT-29 cells were exposed to 50 µM MCN or three mM Necrosatine-1 (Nec-1), a necroptosis preventive. Apoptosis, cell viability, and expression of necroptosis-related genes, including mixed lineage kinase domain-like protein (MLKL), receptor-interacting protein kinase-1 (RIPK1), and receptor-interacting protein kinase-3 (RIPK3), were evaluated. Results: MCN caused a noticeable decline in the survival of HT-29 cells. In contrast to the slight change in the apoptosis index in HT-29 cells, MCN considerably increased the necrosis index. MCN could enhance the expression of MLKL, RIPK1, and RIPK3 in the HT-29 cells. The co-treatment of MCN with Nec-1 resulted in a significant elevation in HT-29 cell survival. Nec-1 could decrease the necrosis index and expression of necroptosis-related proteins in the MCN-exposed HT-29 cells. Conclusions: These findings demonstrated that MCN effectively induced cell death in HT-29 cells by activating the necroptosis pathway.