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Environ Toxicol. 2019 Mar;34(3):233-239. doi: 10.1002/tox.22677. Epub 2018 Nov 15.

Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms.

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Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan.
Institute of Biochemistry, Microbiology, and Immunology, Chung Shan Medical University, Taichung, Taiwan.
Department of Neurology, Division of Internal Medicine, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan.
Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
Research Center of Chinese Herbal Medicine, China Medical University, Taichung, Taiwan.
Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
Department of Parasitology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.


Glioblastoma (GBM) is the most mortality brain cancer in the world. Due to high invasion and drug resistance cause the poor prognosis of GBM. Naringenin, an ingredient of citrus, exhibits many cellular functions such as antioxidant, anti-inflammation, and anticancer. Naringenin inhibits the migration of bladder and lung cancer via modulation of MMP-2 and/or MMP-9 activities, Naringenin inhibits migration and trigger apoptosis in gastric cancer cells through downregulation of AKT pathway. However, the effects of naringenin in GBM still remain to be elucidated. In this study, we reveal the molecular mechanisms of naringenin in the inhibition of migration and invasion in GBM. No overt alternation of cell proliferation was found in of GBM 8901 cells treated with different concentration of naringenin. Slight decreased cell viability was found in GBM 8401 cell treated with 200 and 300 μM naringenin. Significant reduction of migration and invasion as assayed by Boyden chamber analysis was found in of GBM cells treated with 100, 200, and 300 μM naringenin. Zymography analysis also revealed that the activities of MMP-2 and MMP-9 of GBM cells were significantly inhibited in response to 100, 200, or 300 μM naringenin treatment. Proteins of MMP-2 and MMP-9 were downregulated in naringenin treated GBM cells. In addition, naringenin also attenuated the activities of ERK and p38. Naringenin decreased mesenchymal markers (snail and slug) expression as revealed by Western blot analysis. Taken together, our findings indicated that naringenin eliminated the migration and invasion of GBM cells through multiple mechanisms including inhibition of MMPs, ERK, and p38 activities and modulation of EMT markers. Our results also suggested that naringenin may be a potential agent to prevent metastasis of GBM.


glioblastoma; invasion; migration; naringenin

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