Luteolin-induced apoptosis through activation of endoplasmic reticulum stress sensors in pheochromocytoma cells

Kwon,Kisang; Kwon,Young‑Sook; Kim,Seung‑Whan; Yu,Kweon; Lee,Kyung‑Ho; Kwon,O‑Yu

doi:10.3892/mmr.2017.6582

Luteolin-induced apoptosis through activation of endoplasmic reticulum stress sensors in pheochromocytoma cells

Authors:
- Kisang Kwon
- Young‑Sook Kwon
- Seung‑Whan Kim
- Kweon Yu
- Kyung‑Ho Lee
- O‑Yu Kwon
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Affiliations: Department of Biomedical Laboratory Science, College of Health and Welfare, Kyungwoon University, Gumi 39160, Republic of Korea, Department of Nursing, College of Tourism and Health, Joongbu University, Geumsan 32713, Republic of Korea, Department of Emergency Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea, Department of Biological Sciences, College of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea, Department of Anatomy and Cell Biology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea
Published online on: May 12, 2017 https://doi.org/10.3892/mmr.2017.6582
Pages: 380-386

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Abstract

Luteolin [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-chromenone] is an active flavonoid compound from Lonicera japonica (Caprifoliaceae). Luteolin inhibits tumor cell proliferation, inflammatory and oxidative stress better, when compared with other flavonoids. In the present study, it was demonstrated that luteolin induces typical apoptosis in PC12 cells (derived from a pheochromocytoma of the rat adrenal medulla) accompanied by DNA fragmentation and formation of apoptotic bodies. In addition, luteolin regulates expression of the endoplasmic reticulum (ER) chaperone binding immunoglobulin protein, activating ER stress sensors (eukaryotic initiation factor 2α phosphorylation and X‑box binding protein 1 mRNA splicing) and induced autophagy. The results indicated that luteolin induces the upregulation of the unfolded protein response pathway through the ER stress sensors, which helps as an influential regulator for the apoptosis pathway in PC12 cells. The results suggested that the understanding of the molecular mechanisms underlying luteolin‑induced apoptosis may be useful in cancer therapeutics, chemoprevention and neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease.

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