Anat Cell Biol.  2017 Dec;50(4):293-300. 10.5115/acb.2017.50.4.293.

Celecoxib induces cell death on non-small cell lung cancer cells through endoplasmic reticulum stress

• Kim B
• Kim J
• Kim YS

• KMID: 2399898
• DOI: http://doi.org/10.5115/acb.2017.50.4.293

Abstract

Cyclooxygenase-2 (COX-2) is an enzyme induced by various proinflammatory and mitogenic stimuli. Celecoxib is a selective inhibitor of COX-2 that have been shown to affect cell growth and apoptosis. Lung cancer cells expressing COX-2 is able to be a target of celecoxib, this study focuses on investigating that celecoxib induces apoptosis via endoplasmic reticulum (ER) stress on lung cancer cells. We investigated whether celecoxib induced apoptosis on non-small cell lung cancer cell line, A549 and H460. The 50 µM of celecoxib increased apoptotic cells and 100 µM of celecoxib significantly induced apoptosis. To check involvement of caspase cascade, pretreatment of z-VAD-fmk blocked celecoxib-induced apoptosis. However, caspase-3, -8, and -9 were not activated, but cleavage of non-classical caspase-4 was detected using western blot. As checking ER stress associated molecules, celecoxib did not increase expressions of growth arrest and DNA damage inducible protein 34, activating transcription factor 4, and spliced X-box binding protiens-1, but increase of both glucose-regulated protein 78 (GRP78) and C/EBP homologous transcription factor were detected. Salubrinal, inhibitor of eIF2 and siRNA for IRE1 did not alter celecoxib-induced apoptosis. Instead, celecoxib-induced apoptosis might be deeply associated with ER stress depending on GRP78 because siRNA for GRP78 enhanced apoptosis. Taken together, celecoxib triggered ER stress on lung cancer cells and celecoxib-induced apoptosis might be involved in both non-classical caspase-4 and GRP78.

Keyword

Celecoxib; Lung neoplasms; ER stress; Apoptosis

MeSH Terms

Activating Transcription Factor 4
Apoptosis
Blotting, Western
Carcinoma, Non-Small-Cell Lung*
Caspase 3
Celecoxib*
Cell Death*
Cell Line
Cyclooxygenase 2
DNA Damage
Endoplasmic Reticulum Stress*
Endoplasmic Reticulum*
Eukaryotic Initiation Factor-2
Lung Neoplasms
RNA, Small Interfering
Transcription Factors
Activating Transcription Factor 4
Caspase 3
Celecoxib
Cyclooxygenase 2
Eukaryotic Initiation Factor-2
RNA, Small Interfering
Transcription Factors

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