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The tumor-growth inhibitory activity of flavanone and 2′-OH flavanone in vitro and in vivo through induction of cell cycle arrest and suppression of cyclins and CDKs

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Journal of Biomedical Science

Summary

Natural products, including flavonoids, are suggested to be involved in the protective effects of fruits and vegetables against cancer. However, studies concerning the effect of flavonoids frequently lacked data regarding to flavanones. In this study, we investigated the inhibitory effect of flavanone compounds, including flavanone, 2′-OH flavanone, 4′-OH flavanone, 6-OH flavanone, naringin and naringenin, on cell growth of various cancer cells. We determined that flavanone and 2′-OH flavanone inhibited cell growth of A549, LLC, AGS, SK-Hepl and HA22T cancer cells, while other flavanones showed little or no inhibition. We evaluated growth-inhibitory activity of flavanone and 2′-OH flavanone against highly proliferative human lung cancer cells (A549) via anchorage-independent and -dependent colony formation assay, and further showed that treatment of flavanone resulted in a G1 cell cycle arrest with reduction of cyclin D, E and cyclin-dependent kinase (CDK) 2, while treatment of 2′-OH flavanone led to a G2/M phase accumulation with reduction of cyclin B, D and Cdc2. Moreover, we demonstrated the improvement effect of flavanone and 2′-OH flavanone with anti-cancer drug, doxorubicin, on A549 cells. Finally, flavanone and 2′-OH flavanone were evidenced by its inhibition on the growth of A549 and Lewis lung carcinoma cells in vivo.

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Acknowledgments

This study was supported by grants of National Science Council, Republic of China (NSC 94-2311-B-040-005 & NSC 94-2313-B-166-004.)

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Authors and Affiliations

  1. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No 110, Section 1, Chien Kuo N. Road, Taichung, 402, Taiwan

    Yung-Chin Hsiao & Yih-Shou Hsieh

  2. Division of Gastroenterology, Department of Internal Medicine, Armed-Force Taichung General Hospital, Taiping City, Taichung, 411, Taiwan

    Wu-Hsien Kuo

  3. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, No 110, Section 1, Chien Kuo N. Road, Taichung, 402, Taiwan

    Hui-Ling Chiou & Whei-Ling Chiang

  4. Institute of Medicine, Chung Shan Medical University, No 110, Section 1, Chien Kuo N. Road, Taichung, 402, Taiwan

    Shun-Fa Yang

  5. Department of Food Science, Central Taiwan University of Science and Technology, No. 11 Pu-tzu Lane, Pu-tzu Road, Taichung, 406, Taiwan

    Shun-Fa Yang & Shu-Chen Chu

  6. General Education Center, Central Taiwan University of Science and Technology, No.11 Pu-tzu Lane, Pu-tzu Road, Taichung, 406, Taiwan

    Wu-Hsien Kuo

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  1. Yung-Chin Hsiao
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Correspondence to Shu-Chen Chu.

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Yung-Chin Hsiao and Yih-Shou Hsieh are equally contributed to this work.

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Hsiao, YC., Hsieh, YS., Kuo, WH. et al. The tumor-growth inhibitory activity of flavanone and 2′-OH flavanone in vitro and in vivo through induction of cell cycle arrest and suppression of cyclins and CDKs. J Biomed Sci 14, 107–119 (2007). https://doi.org/10.1007/s11373-006-9117-3

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  • DOI: https://doi.org/10.1007/s11373-006-9117-3

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