Université de Bourgogne Franche-Comté, F-21000 Dijon, France.
INSERM Research Center U1231-Cancer and Adaptive Immune Response Team, Bioactive Molecules and Health Research Group, F-21000 Dijon, France.
Cells. 2020 Apr 10;9(4):932. doi: 10.3390/cells9040932.
In spite of chemotherapy and systematic screening for people at risk, the mortality rate of colorectal cancer (CRC) remains consistently high, with 600,000 deaths per year. This low success rate in the treatment of CRC results from many failures associated with high resistance and the risk of metastasis. Therefore, in response to these therapeutic failures, new strategies have been under development for several years aimed at increasing the effect of anticancer compounds and/or at reducing their secondary effects on normal cells, thus enabling the host to better withstand chemotherapy. This study highlights that xanthohumol (Xn) concentrations under the IC values were able to induce apoptosis and to enhance the DNA-damage response (DDR). We demonstrate for the first time that Xn exerts its anticancer activity in models of colon cancer through activation of the ataxia telangiectasia mutated (ATM) pathway. Subsequently, the ability of Xn to restore DNA damage in CRC cells can sensitize them to anticancer agents such as SN38 (7-ethyl-10-hydroxycamptothecin) used in chemotherapy.
尽管进行了化疗和针对高危人群的系统筛查,结直肠癌(CRC)的死亡率仍然居高不下,每年有 60 万人因此死亡。CRC 治疗成功率低是由于多种原因导致的高耐药性和转移风险。因此,针对这些治疗失败,几年来一直在开发新的策略,旨在提高抗癌化合物的效果和/或降低其对正常细胞的次级效应,从而使宿主能够更好地耐受化疗。本研究强调,在 IC 值以下的黄腐酚(Xn)浓度能够诱导细胞凋亡并增强 DNA 损伤反应(DDR)。我们首次证明,Xn 通过激活共济失调毛细血管扩张突变(ATM)途径在结肠癌模型中发挥抗癌活性。随后,Xn 恢复 CRC 细胞中 DNA 损伤的能力可以使它们对化疗中使用的 SN38(7-乙基-10-羟基喜树碱)等抗癌药物敏感。