OncoTargets and Therapy (Apr 2018)

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

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

Journal volume & issue
Vol. Volume 11
pp. 1833 – 1847

Abstract

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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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