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Open AccessArticle

Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis

1
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
2
Department of Dermatology, Yuan’s General Hospital, Kaohsiung 249, Taiwan
3
Department of Evolution, Ecology and Organismal Biology, Ohio State University, Columbus, OH 43212, USA
4
Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(4), 939; https://doi.org/10.3390/ijms19040939
Received: 23 February 2018 / Revised: 14 March 2018 / Accepted: 21 March 2018 / Published: 22 March 2018
(This article belongs to the Special Issue Plant Natural Products for Human Health)
Hinokitiol, a natural monoterpenoid from the heartwood of Calocedrus formosana, has been reported to have anticancer effects against various cancer cell lines. However, the detailed molecular mechanisms and the inhibiting roles of hinokitiol on adenocarcinoma A549 cells remain to be fully elucidated. Thus, the current study was designed to evaluate the effect of hinokitiol on the migration of human lung adenocarcinoma A549 cells in vitro. The data demonstrates that hinokitiol does not effectively inhibit the viability of A549 cells at up to a 10 µM concentration. When treated with non-toxic doses (1–5 µM) of hinokitiol, the cell migration is markedly suppressed at 5 µM. Hinokitiol significantly reduced p53 expression, followed by attenuation of Bax in A549 cells. A dose-dependent inhibition of activated caspase-9 and -3 was observed in the presence of hinokitiol. An observed increase in protein expression of matrix metalloproteinases (MMPs) -2/-9 in A549 cells was significantly inhibited by hinokitiol. Remarkably, when A549 cells were subjected to hinokitiol (1–5 µM), there was an increase in the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in cells. In addition, the incubation of A549 cells with hinokitiol significantly activated the cytochrome c expression, which may be triggered by activation of caspase-9 followed by caspase-3. These observations indicate that hinokitiol inhibited the migration of lung cancer A549 cells through several mechanisms, including the activation of caspases-9 and -3, induction of p53/Bax and antioxidant CAT and SOD, and reduction of MMP-2 and -9 activities. It also induces cytochrome c expression. These findings demonstrate a new therapeutic potential for hinokitiol in lung cancer chemoprevention. View Full-Text
Keywords: A549 cells; hinokitiol; MMPs; p53/Bax; antioxidant enzymes; caspases; migration A549 cells; hinokitiol; MMPs; p53/Bax; antioxidant enzymes; caspases; migration
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MDPI and ACS Style

Jayakumar, T.; Liu, C.-H.; Wu, G.-Y.; Lee, T.-Y.; Manubolu, M.; Hsieh, C.-Y.; Yang, C.-H.; Sheu, J.-R. Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis. Int. J. Mol. Sci. 2018, 19, 939. https://doi.org/10.3390/ijms19040939

AMA Style

Jayakumar T, Liu C-H, Wu G-Y, Lee T-Y, Manubolu M, Hsieh C-Y, Yang C-H, Sheu J-R. Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis. International Journal of Molecular Sciences. 2018; 19(4):939. https://doi.org/10.3390/ijms19040939

Chicago/Turabian Style

Jayakumar, Thanasekaran; Liu, Chao-Hong; Wu, Guan-Yi; Lee, Tzu-Yin; Manubolu, Manjunath; Hsieh, Cheng-Ying; Yang, Chih-Hao; Sheu, Joen-Rong. 2018. "Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis" Int. J. Mol. Sci. 19, no. 4: 939. https://doi.org/10.3390/ijms19040939

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