Melatonin enhances thapsigargin-induced apoptosis through reactive oxygen species-mediated upregulation of CCAAT-enhancer-binding protein homologous protein in human renal cancer cells

Inhibition of ubiquitin-proteasome pathway has been shown to be a promising strategy for the treatment of inflammation and cancer. Here, we show that proteasome inhibitors MG132, PSI-1, and lactacystin induce COX-2 expression via enhancing gene transcription rather than preventing protein degradation in the human alveolar NCI-H292 and A549, and gastric AGS epithelial cells. NF-IL6 and CRE, but not NF-κB elements on the COX-2 promoter were involved in the gene transcription event. The binding of CCAAT/enhancer binding protein (C/EBP)β and C/EBPδ to the CRE and NF-IL6 elements, as well as the recruitment of CBP and the enhancement of histone H3 and H4 acetylation on the COX-2 promoter was enhanced by MG132. However, it did not affect the total protein levels of C/EBPβ and C/EBPδ. MG132-induced DNA-binding activity of C/EBPδ, but not C/EBPβ was regulated by p38, PI3K, Src, and protein kinase C. Small interfering RNA of C/EBPδ suppressed COX-2 expression, further strengthening the role of C/EBPδ in COX-2 gene transcription. In addition, the generation of intracellular reactive oxygen species (ROS) in response to MG132 contributed to the activation of MAPKs and Akt. These findings reveal that the induction of COX-2 transcription induced by proteasome inhibitors requires ROS-dependent protein kinases activation and the subsequent recruitments of C/EBPδ and CBP.

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A synthetic chalcone derivative, 2-hydroxy-3′,5,5′-trimethoxychalcone (DK-139), triggers reactive oxygen species-induced apoptosis independently of p53 in A549 lung cancer cells

Chemico-Biological Interactions ◽

10.1016/j.cbi.2018.11.003 ◽

2019 ◽

Vol 298 ◽

pp. 72-79 ◽

Cited By ~ 3

Author(s):

Ha Na Gil ◽

Euitaek Jung ◽

Dongsoo Koh ◽

Yoongho Lim ◽

Young Han Lee ◽

...

Keyword(s):

Lung Cancer ◽

Reactive Oxygen Species ◽

Cancer Cells ◽

Reactive Oxygen ◽

Lung Cancer Cells ◽

Oxygen Species ◽

Chalcone Derivative ◽

Induced Apoptosis ◽

A549 Lung

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Ethanol extract of Chrysanthemum zawadskii Herbich induces autophagy and apoptosis in mouse colon cancer cells through the regulation of reactive oxygen species

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2688-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Kwang-Youn Kim ◽

Tae-Woo Oh ◽

Hye-Jin Yang ◽

Young-Woo Kim ◽

Jin-Yeul Ma ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Colon Cancer ◽

Cancer Cells ◽

Reactive Oxygen ◽

Ethanol Extract ◽

Oxygen Species ◽

Colon Cancer Cells ◽

Mouse Colon ◽

Induced Apoptosis ◽

Chrysanthemum Zawadskii

Abstract Background Recent research has suggested that autophagy can provide a better mechanism for inducing cell death than current therapeutic strategies. This study investigated the effects of using an ethanol extract of Chrysanthemum zawadskii Herbich (ECZ) to induce apoptosis and autophagy associated with reliable signal pathways in mouse colon cancer CT-26 cells. Methods Using ECZ on mouse colon cancer CT-26 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, reactive oxygen species (ROS) and western blotting were assayed. Results ECZ exhibited cytotoxicity in CT-26 cells in a dose-dependent manner. ECZ induced apoptosis was confirmed by caspase-3 activation, poly (ADP-ribose) polymerase cleavage, and increased production of reactive oxygen species (ROS). Furthermore, it was shown that ECZ induced autophagy via the increased conversion of microtubule-associated protein 1 light chain 3II, the degradation of p62, and the formation of acidic vesicular organelles. The inhibition of ROS production by N-Acetyl-L-cysteine resulted in reduced ECZ-induced apoptosis and autophagy. Furthermore, the inhibition of autophagy by 3-methyladenine resulted in enhanced ECZ-induced apoptosis via increased ROS generation. Conclusion These findings confirmed that ECZ induced ROS-mediated autophagy and apoptosis in colon cancer cells. Therefore, ECZ may serve as a novel potential chemotherapeutic candidate for colon cancer.

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