A Hydroquinone-Based Derivative Elicits Apoptosis and Autophagy via Activating a ROS-Dependent Unfolded Protein Response in Human Glioblastoma

International Journal of Molecular Sciences
S ZappavignaR Filosa

Abstract

5-Lipoxygenase (5-LO) has been reported to be highly expressed in brain tumors and to promote glioma cell proliferation. Therefore, we investigated the anticancer activity of the novel 5-LO inhibitor derivative 3-tridecyl-4,5-dimethoxybenzene-1,2-diol hydroquinone (EA-100C red) on glioblastoma (GBM) cell growth. Cell viability was evaluated by MTT assay. The effects of the compound on apoptosis, oxidative stress and autophagy were assessed by flow cytometry (FACS). The mode of action was confirmed by Taqman apoptosis array, Real Time qPCR, confocal microscopy analysis and the western blotting technique. Our results showed that EA-100C Red had a higher anti-proliferative effect on LN229 as compared to U87MG cells. The compound induced a significant increase of apoptosis and autophagy and up-regulated pro-apoptotic genes (Bcl3, BNIP3L, and NFKBIA) in both GBM cell lines. In this light, we studied the effects of EA-100C red on the expression of CHOP and XBP1, that are implicated in ER-stress-mediated cell death. In summary, our findings revealed that EA-100C red induced ER stress-mediated apoptosis associated to autophagy in GBM cells through CHOP and Beclin1 up-regulation and activation of caspases 3, 9, JNK and NF-kappaB pathway...Continue Reading

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R J BoadoK L Black
Jan 1, 1990·Cancer Chemotherapy and Pharmacology·J L FischelG Milano
Feb 19, 2002·Chemical Reviews·Arkadiusz Kozubek, John H. P. Tyman
Feb 8, 2005·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·P LópezG Ferraro
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Apr 19, 2006·Gastroenterology·Diego F CalvisiSnorri S Thorgeirsson
Jul 14, 2006·Pharmacology & Therapeutics·Oliver Werz, Dieter Steinhilber
Aug 1, 2006·Critical Reviews in Oncology/hematology·Carsten NiederAnca L Grosu
Sep 6, 2006·EMBO Reports·Eva SzegezdiAfshin Samali
Aug 13, 2008·International Journal of Cancer. Journal International Du Cancer·Diego F CalvisiRosa M Pascale
Feb 26, 2010·Expert Opinion on Therapeutic Patents·Carlo Pergola, Oliver Werz
Dec 18, 2010·European Journal of Medicinal Chemistry·Carmen PetronziPaolo de Caprariis
May 13, 2011·Mini Reviews in Medicinal Chemistry·A PedutoR Filosa
Sep 29, 2011·Bioorganic & Medicinal Chemistry·Antonella PedutoRosanna Filosa
May 2, 2013·Journal of Experimental & Clinical Cancer Research : CR·Carmen PetronziRosanna Filosa
Mar 15, 2015·European Journal of Medicinal Chemistry·Rosanna FilosaOliver Werz
Dec 29, 2015·European Journal of Medicinal Chemistry·Antonella PedutoRosanna Filosa
Nov 12, 2016·European Journal of Medicinal Chemistry·Antonella PedutoRosanna Filosa
Apr 6, 2017·International Journal of Molecular Sciences·Wai Chin ChongRajaraman Eri

❮ Previous
Next ❯

Citations

Apr 15, 2020·International Journal of Molecular Sciences·Silvia ZappavignaMichele Caraglia
Feb 27, 2021·Molecular Cancer Therapeutics·Korie A GraysonMichael R King

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
PCR
flow cytometry

Software Mentioned

Quantity One

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis