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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 818261, 13 pages
Research Article

Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo

1Department of Dermatology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
2Department of Child Care, College of Humanities and Social Sciences, Southern Taiwan University, Tainan 71005, Taiwan
3Institute of Biomedical Sciences, College of Life Science, National Chung Hsing University, Taichung 40227, Taiwan
4Agricultural Research Institute, Council of Agriculture Executive, Yuan 10014, Taiwan
5Department of Internal Medicine, Division of Chest Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan
6Department of Medical Education and Research, Taichung-Veterans General Hospital, Taichung 40705, Taiwan
7Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

Received 18 February 2011; Accepted 18 April 2011

Academic Editor: José L. Ríos

Copyright © 2012 Chieh-Shan Wu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Terpinen-4-ol, a monoterpene component of the essential oils of several aromatic plants, exhibits antitumor effects. In this study, the antitumor effects of terpinen-4-ol and the cellular and molecular mechanisms responsible for it were evaluated and studied, respectively on human nonsmall cell lung cancer (NSCLC) cells. Our results indicated that terpinen-4-ol elicited a dose-dependent cytotoxic effect, as determined by MTT assay. Increased sub-G1 population and annexin-V binding, activation of caspases 9 and 3, cleavage of poly(ADPribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated involvement of the mitochondrial apoptotic pathway in terpinen-4-ol-treated A549 and CL1-0 cells. Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. Notably, terpinen-4-ol was able to increase p53 levels in A549 and CL1-0 cells. Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. Moreover, intratumoral administration of terpinen-4-ol significantly suppressed the growth of s.c. A549 xenografts by inducing apoptosis, as confirmed by TUNEL assay. Collectively, these data provide insight into the molecular mechanisms underlying terpinen-4-ol-induced apoptosis in NSCLC cells, rendering this compound a potential anticancer drug for NSCLC.