title: Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.
abstract: Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previousin vitrostudies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, thein vivoeffects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.
authors.affiliation: Department of Radiation Oncology, Taipei City Hospital, Renai Branch, Da'an, Taipei 106, Taiwan, R.O.C.
authors.forename: Jyh-Der
authors.initials: JD
authors.lastname: Leu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Engineering, National Yang-Ming University, Beitou, Taipei 112, Taiwan, R.O.C.
authors.forename: Bo-Shen
authors.initials: BS
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, Tzu Chi University, Hualien 970, Taiwan, R.O.C.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Chiu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Engineering, National Yang-Ming University, Beitou, Taipei 112, Taiwan, R.O.C.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Family Medicine, Taipei City Hospital, Renai Branch, Da'an, Taipei 112, Taiwan, R.O.C.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Electronic Engineering, Hwa-Hsia University of Technology, Zhonghe, Taipei 235, Taiwan, R.O.C.
authors.forename: Fu-Du
authors.initials: FD
authors.lastname: Chen
authors.affiliation: Department of Surgery, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia.
authors.forename: Shiirevnyamba
authors.initials: S
authors.lastname: Avirmed
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Engineering, National Yang-Ming University, Beitou, Taipei 112, Taiwan, R.O.C.; Biophotonics & Molecular Imaging Research Center, National Yang-Ming University, Beitou, Taipei 112, Taiwan, R.O.C.
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
keywords: colorectal cancer; fisetin; radiotherapy; securin; xenograft tumor model