Citrus aurantium L. exhibits apoptotic effects on U937 human leukemia cells partly through inhibition of Akt

Han,Min Ho; Lee,Won Sup; Lu,Jing Nan; Kim,Gonsup; Jung,Jin Myung; Ryu,Chung Ho; Kim,Gi-Young; Hwang,Hye Jin; Kwon,Taeg Kyu; Choi,Yung Hyun

doi:10.3892/ijo.2012.1350

Citrus aurantium L. exhibits apoptotic effects on U937 human leukemia cells partly through inhibition of Akt

Authors:
- Min Ho Han
- Won Sup Lee
- Jing Nan Lu
- Gonsup Kim
- Jin Myung Jung
- Chung Ho Ryu
- Gi-Young Kim
- Hye Jin Hwang
- Taeg Kyu Kwon
- Yung Hyun Choi
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Affiliations: Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School, Busan 614-052, Republic of Korea, Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea, Institute of Life Science and School of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea, Department of Neurosurgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea, Division of Applied Life Science (BK 21 Program), Gyeongsang National University, Jinju 660-701, Republic of Korea , Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea, Department of Food and Nutrition, Dongeui University, Busan 614-714, Republic of Korea, Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea
Published online on: February 1, 2012 https://doi.org/10.3892/ijo.2012.1350
Pages: 2090-2096

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Abstract

Citrus fruits have been used as edible fruits and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are frequently prescribed in concert with other support herbs for many types of disease including cancer. We investigated the anti-proliferative activity of the peels of Citrus aurantium L. along with their effects on apoptosis. We prepared crude methanol extracts of the peels of Citrus aurantium L. (CMEs) and performed experiments using U937 human leukemia cells. The growth of U937 cells was inhibited by CME treatment in a dose-dependent manner, and CME induced caspase-dependent apoptosis. CME inhibited the expression of XIAP and Bcl-xL which are anti-apoptotic proteins. CME inhibited Akt activity in a dose-dependent manner. The apoptotic activity of CME was significantly attenuated by Akt augmentation. In conclusion, this study suggested that CME should induce caspase-dependent apoptosis at least in part through Akt inhibition, providing evidence that CMEs have anticancer activity on human leukemia cells.