Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and -9

Chang,Huai‑Lu; Chang,Yuh‑Ming; Lai,Shih‑Chan; Chen,Ke‑Min; Wang,Kuan‑Chu; Chiu,Tsu‑Ting; Chang,Fu‑Hsin; Hsu,Li‑Sung

doi:10.3892/etm.2016.3994

Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and -9

Authors:
- Huai‑Lu Chang
- Yuh‑Ming Chang
- Shih‑Chan Lai
- Ke‑Min Chen
- Kuan‑Chu Wang
- Tsu‑Ting Chiu
- Fu‑Hsin Chang
- Li‑Sung Hsu
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Affiliations: Department of Thoracic Surgery of Zouying Branch, Kaohsiung Armed Force General Hospital, Kaohsiung 81342, Taiwan, R.O.C., Department of Neurology, Division of Internal Medicine, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan, R.O.C., Department of Parasitology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C., School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C., Department of Biomedical Research, Asia‑Pacific Biotech Developing, Kaohsiung 80681, Taiwan, R.O.C., Institutes of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
Published online on: December 22, 2016 https://doi.org/10.3892/etm.2016.3994
Pages: 739-744

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Abstract

Lung cancer is among the most common causes of cancer‑related mortality. It has a high mortality rate and resistance to chemotherapy due to its high metastatic potential. Naringenin, a bioactive compound identified in several fruits, displays anti‑inflammatory and antitumor effects. Furthermore, naringenin mitigates the migration of several human cancer cell types. However, the effects of naringenin on lung cancer remain unclear. The current study investigated the mechanisms of naringenin on the migration of lung cancer A549 cells. The results indicate that significant alteration in A549 cell proliferation was observed in response to naringenin (0‑300 µM) treatment for 24 and 48 h. Furthermore, a dose‑dependent migration inhibition of A549 in the presence of naringenin was observed by healing and transwell migration assays. In addition, a zymography assay revealed that naringenin exhibited a concentration‑dependent inhibition of matrix metalloproteinase (MMP)‑2 and ‑9 activities. Furthermore, naringenin also inhibited the activities of AKT in a dose‑dependent manner. These observations indicated that naringenin inhibited the migration of lung cancer A549 cells through several mechanisms, including the inhibition of AKT activities and reduction of MMP-2 and -9 activities.