Induction of the cell cycle arrest and apoptosis by flavonoids isolated from Korean Citrus aurantium L. in non-small-cell lung cancer cells |
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| Authors: | Kwang Il Park Hyeon Soo Park Arulkumar Nagappan Gyeong Eun Hong Do Hoon Lee Sang Rim Kang Jin A. Kim Jue Zhang Eun Hee Kim Won Sup Lee Sung Chul Shin Young Sool Hah Gon Sup Kim |
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| Affiliation: | 1. Research Institute of Life Science and College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea;2. Department of Biological Engineering, School of Natural Science, Kyonggi University, Yeongtong, Suwon 443-760, Republic of Korea;3. Korea National Animal Research Resource Center and Korea National Animal Bio-Resource Bank, Gyeongsang National University, Gazwa, Jinju 660-701, Republic of Korea;4. Key Laboratory of Nuclear Medicine of Ministry of Health, Jiangsu Institute of Nuclear Medicine, China;5. Department of Nursing Science, International University of Korea, Jinju 660-759, Republic of Korea;6. Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Gyeongnam Regional Cancer Center, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea;g Department of Chemistry and Research Institute of Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea;h Clinical Research Institute, Gyeongsang National University Hospital, Jinju 660-702, Republic of Korea |
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| Abstract: | This study investigated the anti-proliferative and apoptotic effect of flavonoids isolated from Korean Citrus aurantium L. using A549 lung cancer cells. Flavonoids potently inhibited of A549 cells in a dose-dependent manner, whereas flavonoids had a weak inhibitory effect on proliferation of WI-38 cells. Flow cytometry and Western blot analysis showed that flavonoids induced cell cycle arrest at the G2/M checkpoint by controlling the proteins expression level of cyclin B1, cdc2, cdc25c and p21WAF1/CIP1. Also, flavonoids induced apoptosis through the regulation of the expression of caspases, cleaved PARP and Bax/Bcl-xL ratio. The activity of caspase-3 on A549 cells increased in a dose-dependent manner. These results clearly indicated that the anti-cancer effect of flavonoids on A549 cells follows multiple cellular pathways through G2/M arrest and the induction of apoptosis. |
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| Keywords: | Korean Citrus aurantium L. Flavonoid Human lung cancer cells Cell cycle arrest Apoptosis |
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