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

• Published in: OncoTargets and therapy Vol. 11; pp. 1833 - 1847
• Main Authors: Yu, Xiao, Lin, Hongyan, Wang, Yu, Lv, Wenwen, Zhang, Shuo, Qian, Ying, Deng, Xiaobei, Feng, Nannan, Yu, Herbert, Qian, Biyun
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Dove Medical Press
• Subjects: Analysis; Apoptosis; Biological products; Cancer cells; Cancer research; Citrus; Gene expression; Genes; Health aspects; Lung cancer; Medical schools; Microscopy; Original Research; Polymerase chain reaction; Tumors; lung cancer; apoptosis; d-limonene; autophagy
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S155716

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. 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. 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 gene, suppressed the apoptosis induced by d-limonene. d-limonene may have a therapeutic effect on lung cancer as it can induce apoptosis of lung cancer cells by promoting autophagy.