Anti‐Proliferative Effects of Evodiamine on Human Thyroid Cancer Cell Line ARO |
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Authors: | Meng‐Ching Chen Ching‐Han Yu Shyi‐Wu Wang Hsiao‐Fung Pu Shu‐Fen Kan Lie‐Chwen Lin Chin‐Wen Chi Lary Low‐Tone Ho Chen‐Hsen Lee Paulus S. Wang |
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Affiliation: | 1. Department of Physiology, School of Medicine, National Yang‐Ming University, Taipei City 11221, Taiwan, Republic of China;2. Department of Physiology, School of Medicine, Chung Shan Medical University, Taichung City 40201,Taiwan, Republic of China;3. Department of Physiology and Pharmacology, Chang Gung University, Kwei‐Shan, Taoyuan 33302, Taiwan, Republic of China;4. Department of Herbal Drugs and Natural Products, National Research Institute of Chinese Medicine, Taipei City 11221, Taiwan, Republic of China;5. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei City 11217, Taiwan, Republic of China;6. Department of Surgery, Taipei Veterans General Hospital, Taipei City 11217, Taiwan, Republic of China;7. Department of Medical Research and Education, Taipei City Hospital, Taipei City 10341, Taiwan, Republic of China |
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Abstract: | The incidence of thyroid cancer increases with age, and it is twice in women as common as in men. The undifferentiated thyroid cancer (UTC) is the most aggressive of all thyroid cancers. Unfortunately, there are almost no efficacious therapeutic modalities. It is important to develop some new effective therapies. Evodiamine is a chemical extracted from a kind of Chinese herb named Wu‐Chu‐Yu and has been demonstrated to be effective in preventing the growth of a variety of cancer cells. In the present study, the mechanism by which evodiamine inhibited the undifferentiated thyroid cancer cell line ARO was examined. Based on 3‐(4,5‐dimethylthiazol ‐2‐yle)2,5‐diphenyltetrazolium bromide (MTT) assay, cell proliferation rate was reduced dose‐dependently by evodiamine, but not by rutaecarpine. According to the flow cytometric analysis, evodiamine treatment resulted in G2/M arrest and DNA fragmentation in ARO cells. The G2/M arrest was accompanied with an increase of the expression of cdc25C, cyclin B1, and cdc2‐p161 protein, and it was also with a decrease of the expression of cdc2‐p15. Furthermore, by using the TUNEL assay, evodiamine‐induced apoptosis was observed at 48 h and extended to 72 h. Western blotting demonstrated that evodiamine treatment induced the activation of caspase‐8, caspase‐9, caspase‐3, and the cleavage of poly ADP‐ribose polymerase (PARP). These results suggested that evodiamine inhibited the growth of the ARO cells, arrested them at M phase, and induced apoptosis through caspases signaling. J. Cell. Biochem. 110: 1495–1503, 2010. © 2010 Wiley‐Liss, Inc. |
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Keywords: | evodiamine thyroid cancer cell line ARO G2/M arrest apoptosis |
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