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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