Thiacremonone Augments Chemotherapeutic Agent-Induced Growth Inhibition in Human Colon Cancer Cells through Inactivation of Nuclear Factor-κB
Thiacremonone Augments Chemotherapeutic Agent-Induced Growth Inhibition in Human Colon Cancer Cells through Inactivation of Nuclear Factor-κB
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DOI：
10.1158/1541-7786.mcr-08-0580
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发表时间：
2009-06-01
影响因子：
5.2
通讯作者：
Hong, Jin Tae
中科院分区：
文献类型：
--
作者：
Ban, Jung Ok;Lee, Hee Soon;Hong, Jin Tae
化疗策略通常使用多种药物来克服耐药和降低药物毒性。核因子κ B （nf - κ B）的激活与癌细胞的耐药有关。此前，我们报道了一种从大蒜中分离的新型硫化合物thiacremonone在结肠癌细胞中抑制NF-kappa B和癌细胞的生长，IC50值约为100 μ g/mL。在本研究中，我们通过对NF-kappa b的失活来检测硫肾上腺素是否会增加癌细胞对化疗药物的敏感性。结肠癌细胞用硫肾上腺素（50 μ g/mL， IC50的一半剂量）和较低剂量的每种化疗药物（IC50的一半剂量）共处理24小时。用硫肾上腺素和多西紫杉醇联合处理的细胞中NF-kappa B活性完全消失，而硫肾上腺素本身不改变NF-kappa B活性。在结肠癌和其他癌细胞中，与其他抗癌药物也发现了这种联合药物效应。与抑制细胞生长和NF-kappa B活性良好相关的是，联合处理还调节NF-kappa B靶基因。硫肾上腺素（1 mg/kg）灌胃小鼠4周，可显著增强多西他赛（1 mg/kg， 1次，4次）诱导的肿瘤生长减少，并调节nf - κ B活性和nf - κ B靶基因。这些结果保证了精心设计的临床研究，以调查硫肾上腺素和常用化疗药物联合用于治疗人类癌症。[j] .癌症杂志，2009;7(6):870-9。
Chemotherapeutic strategies commonly use multiple agents to overcome drug resistance and to lower drug toxicity. Activation of nuclear factor-kappa B (NF-kappa B) is implicated in drug resistance in cancer cells. Previously, we reported that thiacremonone, a novel sulfur compound isolated from garlic, inhibited NF-kappa B and cancer cell growth with IC50 values about 100 mu g/mL in colon cancer cells. In the present study, we tested whether thiacremonone could increase susceptibility of cancer cells to chemotherapeutics through inactivation of NF-kappa B. Colon cancer cells were cotreated with thiacremonone (50 mu g/mL, half dose of IC50) and lower doses of each chemotherapeutic agent (half dose of IC50) for 24 hours. NF-kappa B activity was completely abrogated in cells treated with a combination of thiacremonone and docetaxel, whereas thiacremonone on its own did not alter NF-kappa B activity. This combined drug effect was also found with other anticancer drugs in colon cancer and in other cancer cells. In good correlation with inhibition of cell growth and NF-kappa B activity, the combination treatment also regulated NF-kappa B target genes. Oral treatment of mice with thiacremonone (1 mg/kg) by administering it in drinking water for 4 weeks significantly augmented docetaxel (1 mg/kg, i.p., four times)induced decrease of tumor growth accompanied with regulation of NF-kappa B activity and NF-kappa B target genes. These results warrant carefully designed clinical studies investigating the combination of thiacremonone and commonly used chemotherapeutic agents for the treatment of human cancers. (Mol Cancer Res 2009;7(6):870-9)