title: Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo.
abstract: 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.
authors.affiliation: Department of Dermatology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Chieh-Shan
authors.initials: CS
authors.lastname: Wu
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
authors.forename: Jeng-Jer
authors.initials: JJ
authors.lastname: Shieh
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Huang
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Lin
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.forename: Jinghua-Tsai
authors.initials: JT
authors.lastname: Chang
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin