A Combination of δ-Tocotrienol and Ferulic Acid Synergistically Inhibits Telomerase Activity in DLD-1 Human Colorectal Adenocarcinoma Cells
A Combination of δ-Tocotrienol and Ferulic Acid Synergistically Inhibits Telomerase Activity in DLD-1 Human Colorectal Adenocarcinoma Cells
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DOI：
10.3177/jnsv.62.281
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发表时间：
2016-10-01
影响因子：
1.6
通讯作者：
Miyazawa, Teruo
中科院分区：
文献类型：
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作者：
Eitsuka, Takahiro;Tatewaki, Naoto;Miyazawa, Teruo
米糠是功能化合物的丰富来源，包括生育三烯醇（T3）和阿魏酸（FA）。我们之前研究了T3的抗癌特性，并报道了delta-T3对血管生成和端粒酶活性的有效抑制作用。在本研究中，我们考察了delta-T3和FA联合使用对DLD-1人结直肠癌细胞端粒酶活性的协同抑制作用。与单独治疗相比，delta-T3和FA联合治疗显著降低了细胞端粒酶活性，而FA单独治疗没有抑制作用。delta-T3和FA共处理还能协同下调端粒酶的催化亚基——人端粒酶逆转录酶（hTERT）的表达，说明端粒酶的酶活性在转录水平受到控制。FA显著提高了细胞内delta-T3的浓度，说明FA提高了delta-T3的生物利用度，从而提高了delta-T3对端粒酶的抑制效力。FA可能是增强δ - t3抗癌活性的有希望的候选物。
Rice bran is a rich source of functional compounds, including tocotrienol (T3) and ferulic acid (FA). We previously investigated the anti-cancer properties of T3, and reported on the potent inhibitory effects of delta-T3 on angiogenesis and telomerase activity. In this study, we examined the synergistic suppressive effects of the combination of delta-T3 and FA on telomerase activity in DLD-1 human colorectal adenocarcinoma cells. Co-treatment with delta-T3 and FA significantly decreased cellular telomerase activity compared to treatment with delta-T3 alone, whereas FA alone had no inhibitory effect. Co-treatment with delta-T3 and FA also synergistically down-regulated the expression of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, indicating that the enzymatic activity of telomerase is controlled at the transcriptional level. FA significantly increased the intracellular concentration of delta-T3, suggesting that FA improved the bioavailability of delta-T3, thereby increasing the inhibitory potency of delta-T3 on telomerase. FA may be a promising candidate for augmenting the anti-cancer activity of delta-T3.