Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
J Nutr Biochem. 2023 Nov;121:109430. doi: 10.1016/j.jnutbio.2023.109430. Epub 2023 Aug 18.
Apigenin, a flavonoid that widely existed in vegetables and fruits, possesses anticarcinogenic, low toxicity, and no mutagenic properties, suggesting that apigenin is a potential therapeutic agent for tumors. However, the underlying anti-cancer molecular target of apigenin is still unclear. Therefore, to reveal the direct target and amino acid site of apigenin against colorectal cancer is the focus of this study. In the present study, the results proved that the anti-CRC activity of apigenin was positively correlated with pyruvate kinase M2 (PKM2) expression, characterized by the inhibition of cell proliferation and increase of apoptotic effects induced by apigenin in LS-174T cells of knock down PKM2. Next, pull-down and MALDI-TOF/TOF analysis determined that apigenin might interact directly with PKM2 in HCT-8 cells. Further, the study confirmed that lysine residue 433 (K433) was a key amino acid site for PKM2 binding to apigenin. Apigenin restricted the glycolysis of LS-174T and HCT-8 cells by targeting the K433 site of PKM2, thereby playing an anti-CRC role in vivo and in vitro. Meanwhile, apigenin markedly attenuated tumor growth without any adverse effects. Taken together, these findings reveal that apigenin is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC.
芹菜素是一种广泛存在于蔬菜和水果中的类黄酮，具有抗癌、低毒性和非致突变性，表明芹菜素是一种有潜力的肿瘤治疗药物。然而，芹菜素的潜在抗癌分子靶点尚不清楚。因此，揭示芹菜素针对结直肠癌的直接靶标和氨基酸位点是本研究的重点。在本研究中，结果证明芹菜素的抗 CRC 活性与丙酮酸激酶 M2（PKM2）表达呈正相关，表现在敲低 PKM2 的 LS-174T 细胞中，芹菜素抑制细胞增殖并增加凋亡作用。接下来，下拉和 MALDI-TOF/TOF 分析确定芹菜素可能在 HCT-8 细胞中直接与 PKM2 相互作用。进一步的研究证实，赖氨酸残基 433（K433）是 PKM2 与芹菜素结合的关键氨基酸位点。芹菜素通过靶向 PKM2 的 K433 位点限制 LS-174T 和 HCT-8 细胞的糖酵解，从而在体内和体外发挥抗 CRC 作用。同时，芹菜素显著抑制肿瘤生长而没有任何不良反应。总之，这些发现表明，芹菜素作为一种有前途的 PKM2 抑制剂，值得考虑用于预防 CRC。
