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    題名: Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse
    作者: Chen, Y.J.
    Liao, H.F.
    Tsai, T.H.
    Wang, SY
    Shiao, MS
    貢獻者: 運教所
    關鍵詞: caffeic acid phenethyl ester (CAPE)
    radiosensitization
    colorectal adenocarcinoma
    glutathione
    NF-kappa B
    bone marrow
    日期: 2005
    上傳時間: 2009-11-12 13:45:33 (UTC+8)
    摘要: Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity.
    Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-kappa B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points.

    Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or gamma-glutamyl transpeptidase activity. Radiation activated NF-kappa B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity.

    Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-kappa B activity, without toxicity to bone marrow, liver, and kidney. (c) 2005 Elsevier Inc.
    關聯: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Volume: 63 Issue: 4 Pages: 1252-1261
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