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D-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer

Authors Yu X, Lin H, Wang Y, Lv W, Zhang S, Qian Y, Deng X, Feng N, Yu H, Qian B

Received 1 November 2017

Accepted for publication 6 February 2018

Published 4 April 2018 Volume 2018:11 Pages 1833—1847

DOI https://doi.org/10.2147/OTT.S155716

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Ingrid Espinoza


Xiao Yu,1,* Hongyan Lin,1,* Yu Wang,1 Wenwen Lv,1 Shuo Zhang,1 Ying Qian,1 Xiaobei Deng,1 Nannan Feng,1 Herbert Yu,2 Biyun Qian1

1Hongqiao International Institute of Medicine, Shanghai Tongren Hospital & Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA

*These authors contributed equally to this work

Purpose: D-limonene is a plant extract with widespread application, and it has been recently reported to have antiproliferative and proapoptotic effects on cancer cells. However, the mechanisms by which D-limonene achieves these effects, especially in lung cancer, are not entirely clear. Therefore, the goal of this study was to examine the effects of D-limonene on lung cancer and explore its mechanisms of action.
Methods: We examined the therapeutic effects of D-limonene on lung cancer cells and in a xenograft animal model by characterizing its effects on the pathways of apoptosis and autophagy. Cell proliferation was measured using the Cell Counting Kit-8, and apoptosis was determined by flow cytometric analysis. Levels of LC3 puncta, an autophagy marker, were analyzed by laser scanning confocal microscopy. Autophagy and apoptosis-related gene expression were assessed by real-time quantitative polymerase chain reaction and Western blot.
Results: D-limonene inhibited the growth of lung cancer cells and suppressed the growth of transplanted tumors in nude mice. Expression of apoptosis and autophagy-related genes were increased in tumors after treatment with D-limonene. Furthermore, the use of chloroquine, an autophagy inhibitor, and knockdown of the atg5 gene, suppressed the apoptosis induced by D-limonene.
Conclusion: D-limonene may have a therapeutic effect on lung cancer as it can induce apoptosis of lung cancer cells by promoting autophagy.

Keywords: D-limonene, lung cancer, apoptosis, autophagy
 

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