Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells.

Black raspberry components inhibit proliferation, induce apoptosis, and modulate gene expression in rat esophageal epithelial cells.
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DOI:
10.1080/01635580903285148
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发表时间:
2009
期刊:
Nutrition and cancer
影响因子:
--
通讯作者:
Stoner GD
Stoner GD
中科院分区:
其他
文献类型:
--
作者:
Zikri NN;Riedl KM;Wang LS;Lechner J;Schwartz SJ;Stoner GD

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我们已经证明,含有冻干黑树莓(BRB)的饮食可以抑制化学诱导的大鼠食道癌症的发展。为了深入了解BRB抑制食管癌发生的可能机制,我们评估了BRB的乙醇(EtOH)提取物和BRB中的两种成分花青素(花青素-3- o -葡萄糖苷和花青素-3- o - rutino苷)对大鼠食管上皮细胞系生长、凋亡和基因表达的影响。EtOH提取物和两种花青素在高致瘤细胞系(RE-149 DHD)中选择性地抑制生长和诱导凋亡,而在弱致瘤细胞系(RE-149)中无明显作用。EtOH提取物对RE-149 DHD细胞花青素的吸收远远超过其对RE-149 DHD细胞的吸收,这可能解释了提取物对RE-149 DHD细胞生长和凋亡的选择性作用。每日在培养基中添加乙醇提取物和花青素,可增强细胞的生长抑制和促凋亡作用。有趣的是,EtOH提取物并未改变RE-149 DHD细胞中环氧合酶-2 (COX-2)和一氧化氮合酶(i-NOS)的表达,而花青素均下调了这些基因的表达。这种差异效应可能与提取物中花青素的相对含量与单独添加到培养基中有关。我们得出结论,EtOH提取物对体外高致瘤性大鼠食管上皮细胞生长和凋亡的选择性作用可能是由于其成分花青素的优先吸收和保留,这也可能是冻干全莓对体内肿瘤细胞有更大抑制作用的原因。
We have shown that a diet containing freeze-dried black raspberries (BRB) inhibits the development of chemically-induced cancer in the rat esophagus. To provide insights into possible mechanisms by which BRB inhibit esophageal carcinogenesis, we evaluated an ethanol (EtOH) extract of BRB, and two component anthocyanins (cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside) in BRB, for their effects on growth, apoptosis and gene expression in rat esophageal epithelial cell lines. The EtOH extract and both anthocyanins selectively caused significant growth inhibition and induction of apoptosis in a highly tumorigenic cell line (RE-149 DHD) but not in a weakly tumorigenic line (RE-149). The uptake of anthocyanins from the EtOH extract into RE-149 DHD cells far exceeded their uptake into RE-149 cells, which may have accounted for the selective effects of the extract on growth and apoptosis of RE-149 DHD cells. The growth inhibitory and pro-apoptotic effects were enhanced by the daily addition of the EtOH extract and the anthocyanins to the medium. Interestingly, the EtOH extract did not alter cyclooxygenase-2 (COX-2) and nitric oxide synthase (i-NOS) expression in RE-149 DHD cells whereas, both anthocyanins down-regulated the expressions of these genes. This differential effect may have been related to the relative amounts of anthocyanins in the extract versus when they were added individually to the medium. We conclude that the selective effects of the EtOH extract on growth and apoptosis of highly tumorigenic rat esophageal epithelial cells in vitro may be due to preferential uptake and retention of its component anthocyanins, and this may also be responsible for the greater inhibitory effects of freeze-dried whole berries on tumor cells in vivo.
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