You Shen, Wang Ming-Jin, Hou Zhen-Yan, Wang Wei-Da, Du Ting-Ting, Xue Ni-Na, Ji Ming, Chen Xiao-Guang
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Pharmaceuticals (Basel). 2023 Jun 14;16(6):877. doi: 10.3390/ph16060877.
Chlorogenic acid (CHA) has been shown to have substantial biological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, the pharmacological role of CHA in neuroblastoma has not yet been assessed. Neuroblastoma is a type of cancer that develops in undifferentiated sympathetic ganglion cells. This study aims to assess the antitumor activity of CHA against neuroblastoma and reveal its mechanism of action in cell differentiation.
Be(2)-M17 and SH-SY5Y neuroblastoma cells were used to confirm the differentiation phenotype. Subcutaneous and orthotopic xenograft mouse models were also used to evaluate the antitumor activity of CHA. Seahorse assays and metabolomic analyses were further performed to investigate the roles of CHA and its target ACAT1 in mitochondrial metabolism.
CHA induced the differentiation of Be(2)-M17 and SH-SY5Y neuroblastoma cells in vivo and in vitro. The knockdown of mitochondrial ACAT1, which was inhibited by CHA, also resulted in differentiation characteristics in vivo and in vitro. A metabolomic analysis revealed that thiamine metabolism was involved in the differentiation of neuroblastoma cells.
These results provide evidence that CHA shows good antitumor activity against neuroblastoma via the induction of differentiation, by which the ACAT1-TPK1-PDH pathway is involved. CHA is a potential drug candidate for neuroblastoma therapy.
绿原酸（CHA）已被证明具有多种生物学活性，包括抗炎、抗氧化和抗肿瘤作用。然而，CHA在神经母细胞瘤中的药理作用尚未得到评估。神经母细胞瘤是一种发生于未分化交感神经节细胞的癌症。本研究旨在评估CHA对神经母细胞瘤的抗肿瘤活性，并揭示其在细胞分化中的作用机制。
使用Be(2)-M17和SH-SY5Y神经母细胞瘤细胞来确认分化表型。还使用皮下和原位异种移植小鼠模型来评估CHA的抗肿瘤活性。进一步进行海马实验和代谢组学分析，以研究CHA及其靶点ACAT1在线粒体代谢中的作用。
CHA在体内和体外均诱导了Be(2)-M17和SH-SY5Y神经母细胞瘤细胞的分化。线粒体ACAT1的敲低（被CHA抑制）在体内和体外也导致了分化特征。代谢组学分析表明硫胺素代谢参与了神经母细胞瘤细胞的分化。
这些结果提供了证据，表明CHA通过诱导分化对神经母细胞瘤显示出良好的抗肿瘤活性，其中涉及ACAT1-TPK1-PDH途径。CHA是神经母细胞瘤治疗的潜在候选药物。
