Naringin Combined with NF-κB Inhibition and Endoplasmic Reticulum Stress Induces Apoptotic Cell Death Via Oxidative Stress and the PERK/eIF2α/ATF4/CHOP Axis in HT29 Colon Cancer Cells

Overview

Journal Biochem Genet

Specialty Molecular Biology

Date 2020 Sep 26

PMID 32979141

Citations 10

Authors

Dogan Albayrak

Oguzhan Doganlar

Suat Erdogan

Meryem Merakli

Ayten Dogan

Pelin Turker

Ayten Bostanci

Zeynep Banu Doganlar

Affiliations

Soon will be listed here.

Abstract

Currently, 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-κB 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/eIF2α/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/eIF2α/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.

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