The novel NF-κB inhibitor DHMEQ synergizes with celecoxib to exert antitumor effects on human liver cancer cells by a ROS-dependent mechanism

Cancer Letters
Nadia LampiasiMelchiorre Cervello

Abstract

In a previous work of ours dehydroxymethyl-epoxyquinomicin (DHMEQ), an inhibitor of NF-κB, was shown to induce apoptosis through Reactive Oxygen Species (ROS) production in hepatoma cells. The present study demonstrated that DHMEQ cooperates with Celecoxib (CLX) to decrease NF-κB DNA binding and to inhibit cell growth and proliferation more effectively than treatment with these single agents alone in the hepatoma cell lines HA22T/VGH and Huh-6. ROS production induced by the DHMEQ-CLX combination in turn generated the expression of genes involved in endoplasmic reticulum (ER) stress and silencing TRB3 mRNA significantly decreased DHMEQ-CLX-induced cell growth inhibition. Moreover, the DHMEQ-CLX combination was associated with induction of PARP cleavage and down-regulation of the anti-apoptotic proteins Bcl-2, Mcl-1 and survivin, as well as activated Akt. CD95 and CD95 ligand expression increased synergistically in the combination treatment, which was reversed in the presence of NAC. Knockdown of CD95 mRNA expression significantly decreased DHMEQ-CLX-induced cell growth inhibition in both cell lines. These data suggest that the DHMEQ-CLX combination kills hepatoma cells via ROS production, ER stress response and the activation of...Continue Reading

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Citations

Sep 13, 2013·Toxins·Adrian LupescuFlorian Lang
Feb 13, 2014·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Hee Jung KimYoung Tae Kim
Apr 1, 2013·Clinical Journal of Gastroenterology·Kazuhiro Nouso
Feb 9, 2016·Biochimie·Debasis MondalPartha K Chandra
Aug 11, 2015·The Journal of Pharmacy and Pharmacology·Tangbadioa H CoulidiatiDemetrius A M Araújo
Nov 21, 2015·Molecular Cancer·C SanhuezaA F G Quest
Oct 14, 2017·Marine Drugs·Cinzia CalcabriniCarmela Fimognari
Apr 16, 2016·International Journal of Molecular Medicine·Magdy El-Salhy, Kazuo Umezawa
May 10, 2020·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·M F CandidoMaría Sol Brassesco
Mar 5, 2013·Oncotarget·James A McCubreyZoya N Demidenko
Jun 2, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Aeju LeePaolo Decuzzi
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eman M OthmanAhmed Wahid
Oct 11, 2017·Journal of Medicinal Chemistry·Zhangjian HuangYihua Zhang

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