Naringin Combined with NF-?B Inhibition and Endoplasmic Reticulum Stress Induces Apoptotic Cell Death via Oxidative Stress and the PERK/eIF2?/ATF4/CHOP Axis in HT29 Colon Cancer Cells

Albayrak, DoganDoganlar, OguzhanErdogan, SuatMerakli, MeryemDogan, AytenTurker, PelinBostanci, Ayten2024-06-122024-06-1220210006-29281573-4927https://doi.org/10.1007/s10528-020-09996-5https://hdl.handle.net/20.500.14551/22646Currently, combination therapy is considered the most effective solution for a selective chemotherapeutic effect in the treatment of colon cancer. This study investigated the death of both colon cancer HT29 cells and healthy vascular smooth muscle TG-Ha-VSMC cells (VSMCs) induced by naringin combined with endoplasmic reticulum (ER) stress and NF-kappa B inhibition. Naringin combined with tunicamycin and BAY 11-7082 suppressed the proliferation of HT29 cells in a dose-dependent manner and induced particularly apoptotic death without significantly affecting healthy VSMCs according to Annexin V/PI staining and AO/EB staining analyses. Insufficient antioxidant defense and heat shock response as well as excessive ROS generation were observed in HT29 cells following combination therapy. Quantitative real-time PCR and western blot analysis demonstrated that drug combination-induced mitochondrial apoptosis was activated through the ROS-mediated PERK/eIF2 alpha/ATF4/CHOP pathway. Additionally, naringin combination significantly reduced the sXBP expression induced by tunicamycin+BAY 11-7082 in a dose-dependent manner. In conclusion, this study found that naringin combined with tunicamycin+BAY 11-7082 efficiently induced apoptotic cell death in HT29 colon cancer cells via oxidative stress and the PERK/eIF2 alpha/ATF4/CHOP pathway, suggesting that naringin combined with tunicamycin plus BAY 11-7082 could be a new combination therapy strategy for effective colon cancer treatment with minimal side effects on healthy cells.en10.1007/s10528-020-09996-5info:eu-repo/semantics/closedAccessNaringinTunicamycinBAY 11-7082ER StressApoptosisColon CancerUnfolded Protein ResponseEr StressMitochondrial ApoptosisSignaling PathwayLeukemia-CellsActivationCarcinomaGrowthExpressionArrestNaringin Combined with NF-?B Inhibition and Endoplasmic Reticulum Stress Induces Apoptotic Cell Death via Oxidative Stress and the PERK/eIF2?/ATF4/CHOP Axis in HT29 Colon Cancer CellsArticle591159184Q4WOS:0005728665000012-s2.0-8509142299832979141Q2