Anti-proliferate and pro-apoptotic effects of 2,3-Dihydro-3,5,dihydroxy-6-methyl-4H-pyranone through inactivation of NF-κB in human colon cancer cells
Anti-proliferate and pro-apoptotic effects of 2,3-Dihydro-3,5,dihydroxy-6-methyl-4H-pyranone through inactivation of NF-κB in human colon cancer cells
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DOI：
10.1007/bf02977371
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发表时间：
2007-11-01
影响因子：
6.7
通讯作者：
Hong, Jin Tae
中科院分区：
文献类型：
--
作者：
Ban, Jung Ok;Hwang, In Gulk;Hong, Jin Tae
许多天然化合物已被证明通过转录因子的氧化还原调节来防止癌细胞生长。NF-κ B B是一种氧化还原转录因子，与多种癌细胞的凋亡有关。本研究检测了从洋葱中分离的2，3-二氢-3，5-二羟基-6-甲基-4H-吡喃酮（DAPK）是否可以调节NF-κ B的活性，从而诱导结肠癌细胞的凋亡。用不同浓度（0.5-1.5 mg/mL）的DALLY处理不同时间（0-48 h）抑制结肠癌细胞（SW 620和HCT 116）的生长，随后以剂量依赖性方式诱导凋亡。还发现，地塞米松调节肿瘤坏死因子-α（TNF-α）和十四烷酰佛波醇乙酸酯（TPA）诱导的NF-κ B转录和DNA结合活性。此外，DIFFERENTIAL抑制NF-κ B B靶向抗凋亡基因（Bcl-2），而它诱导凋亡基因（Bax，裂解的caspase-3和裂解的PARP）的表达。这些结果表明，来自洋葱的DIFFERENTIAL通过抑制NF-κ B诱导凋亡性细胞死亡来抑制结肠癌细胞生长。
Many natural compounds have been shown to prevent cancer cell growth through the redox regulation of transcription factors. NF-kappa B, a redox transcription factor, has been implicated in the apoptotic cell death of several cancer cells. This study examined whether or nor 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone (DDMP) isolated from onions can modulate the activity of NF-kappa B, thereby induce the apoptotic cell death of colon cancer cells. Treatment with different DDMP concentrations (0.5-1.5 mg/mL) for various periods (0-48 h) inhibited the growth of colon cancer cells (SW620 and HCT116) followed by the induction of apoptosis in a dose dependent manner. It was also found that DDMP modulated tumor necrosis factor-a (TNF-alpha) and tetradeanoyl phorbol acetate (TPA)-induced NF-kappa B transcriptional and DNA binding activity. Moreover, DDMP suppressed the NF-kappa B target anti-apoptotic genes (Bcl-2), whereas it induced the expression of the apoptotic genes (Bax, cleaved caspase-3 and cleaved PARP). These results suggest that DDMP from onions inhibit colon cancer cell growth by inducing apoptotic cell death through the inhibition of NF-kappa B.