Department of Clinical Laboratory, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
Biometals. 2018 Oct;31(5):797-805. doi: 10.1007/s10534-018-0123-5. Epub 2018 Jun 27.
Colorectal cancer (CRC) is one of the most common malignancies worldwide, and new treatment strategies for CRC are required because of the existing chemotherapy resistance. Iron chelators, which have been used widely for the treatment of iron-overload disease, were reported to exert anti-proliferative effects in cancer. However, the role of iron chelation in CRC was largely unknown. In this study, we found that the iron chelator DFO inhibited CRC cell growth significantly. In addition, the gene expression profile was greatly changed by DFO treatment, and many cell growth-related genes were dysregulated. Further study showed that DFO induced a significant increase in global histone methylation in CRC cells. However, the levels of histone methyltransferases and histone demethylases did not change in response to DFO treatment, implying that the enzymatic activity of these enzymes might be regulated by iron chelation. In conclusion, this study reveals a novel role for DFO in CRC cell growth, and is the first to demonstrate that global histone methylation is modulated by iron chelation in CRC cells.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一，由于存在化疗耐药性，需要新的 CRC 治疗策略。铁螯合剂已广泛用于治疗铁过载疾病，据报道其在癌症中具有抗增殖作用。然而，铁螯合在 CRC 中的作用在很大程度上尚不清楚。在这项研究中，我们发现铁螯合剂去铁胺（DFO）可显著抑制 CRC 细胞生长。此外，DFO 处理极大地改变了基因表达谱，许多与细胞生长相关的基因失调。进一步的研究表明，DFO 诱导 CRC 细胞中组蛋白整体甲基化显著增加。然而，组蛋白甲基转移酶和组蛋白去甲基酶的水平并未因 DFO 处理而改变，这表明这些酶的酶活性可能受到铁螯合的调节。总之，本研究揭示了 DFO 在 CRC 细胞生长中的新作用，并且首次证明铁螯合可调节 CRC 细胞中的整体组蛋白甲基化。
