Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells
| Autor: | Aditi Banerjee, Vivekjyoti Banerjee, Thomas G. Blanchard, Steven J. Czinn |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death medicine.medical_specialty Cell Survival Andrographolide Antineoplastic Agents Apoptosis Caspase 3 Biology chemotherapy Antioxidants 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Internal medicine medicine Humans Cell Proliferation Membrane Potential Mitochondrial reactive oxygen species chemistry.chemical_classification Reactive oxygen species Endoplasmic reticulum andrographolide Cell Cycle Checkpoints unfolded protein response Endoplasmic Reticulum Stress Gene Expression Regulation Neoplastic Oxidative Stress 030104 developmental biology Endocrinology Oncology chemistry 030220 oncology & carcinogenesis Colonic Neoplasms Cancer cell Cancer research Unfolded protein response Diterpenes Oxidation-Reduction Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.15393 |
| Popis: | // Aditi Banerjee 1 , Vivekjyoti Banerjee 1 , Steven Czinn 1 , Thomas Blanchard 1 1 Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, U.S.A Correspondence to: Aditi Banerjee, email: abanerjee@peds.umaryland.edu Keywords: andrographolide, chemotherapy, reactive oxygen species, endoplasmic reticulum stress, unfolded protein response Received: August 15, 2016 Accepted: January 30, 2017 Published: February 16, 2017 ABSTRACT Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well. |
| Databáze: | OpenAIRE |
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