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

Chieh-Shan Wu; Yun-Ju Chen; Jeremy J. W. Chen; Jeng-Jer Shieh; Chia-Hsin Huang; Pei-Shan Lin; Gee-Chen Chang; JingHua-Tsai Chang; Chi-Chen Lin

doi:10.1155/2012/818261

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

Journal

Evidence-Based Complementary and Alternative Medicine

Journal Volume

2012

Pages

1-13

Date Issued

2012

Date

2012

Author(s)

Chieh-Shan Wu

Yun-Ju Chen

Jeremy J. W. Chen

Jeng-Jer Shieh

Chia-Hsin Huang

Pei-Shan Lin

Gee-Chen Chang

JingHua-Tsai Chang

Chi-Chen Lin

DOI

10.1155/2012/818261

URI

https://scholars.tari.gov.tw/handle/123456789/14336

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.

Publisher

Oxford University Press

Type

journal article

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