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
Küçük Resim Yok
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer/Plenum Publishers
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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-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.
Açıklama
Anahtar Kelimeler
Naringin, Tunicamycin, BAY 11-7082, ER Stress, Apoptosis, Colon Cancer, Unfolded Protein Response, Er Stress, Mitochondrial Apoptosis, Signaling Pathway, Leukemia-Cells, Activation, Carcinoma, Growth, Expression, Arrest
Kaynak
Biochemical Genetics
WoS Q Değeri
Q4
Scopus Q Değeri
Q2
Cilt
59
Sayı
1
