Liu Lin, Xing Gang, Guo Xiaoyi, Chen Hui, Li Jian, Wang Jian, Li Yaling, Liang Gang, Liu Minghua
School of Pharmacy, Southwest Medical University, Luzhou, China.
Drug Dispending Department, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
Front Pharmacol. 2025 Apr 16;16:1552486. doi: 10.3389/fphar.2025.1552486. eCollection 2025.
Exploring the anti-tumor molecular mechanisms of traditional Chinese medicines has become an important strategy to develop novel anti-tumor drugs in the clinic. Several pharmacological studies have reported the antioxidant, antibacterial, anti-inflammatory, and anti-tumor effects of clove. Previously, we have shown that the active fraction from clove (AFC) can inhibit the growth of tumor cells, particularly colon cancer cells, . However, the mechanism of action regarding the anti-colon cancer activity of AFC, especially in aerobic glycolysis, has not been adequately investigated. In this study, we found that AFC significantly inhibited the growth of five types of colon cancer cells, downregulated the mRNA and protein levels of M2-type pyruvate kinase (PKM2), and reduced aerobic glycolysis capacity. Transfection of PKM2-siRNA mimicked the inhibitory effects of AFC on aerobic glycolysis in colon cancer cells. Furthermore, the highly expressed, tumor-specific targets c-myc and cyclin D1 in cells were also found to be downregulated following the action of AFC. In the HCT116 cell xenograft nude mice models, the results after AFC administration were consistent with those of the cellular experiments, while AFC caused less liver injury and weight loss than the conventional chemotherapeutic agent 5- fluorouracil (5-FU). In conclusion, AFC inhibits colon cancer growth by downregulating PKM2 to inhibit aerobic glycolysis and reduce the tumor-specific high expression of c-myc and cyclin D1. Future work should explore how it downregulates pyruvate kinase (PK) in the first place, along with the intrinsic mechanism between the downregulation of PKM2 and the downregulation of c-myc.
探索中药的抗肿瘤分子机制已成为临床上开发新型抗肿瘤药物的重要策略。多项药理研究报道了丁香的抗氧化、抗菌、抗炎和抗肿瘤作用。此前，我们已经表明，丁香活性成分（AFC）可以抑制肿瘤细胞的生长，尤其是结肠癌细胞。然而，关于AFC抗结肠癌活性的作用机制，特别是在有氧糖酵解方面，尚未得到充分研究。在本研究中，我们发现AFC显著抑制五种结肠癌细胞的生长，下调M2型丙酮酸激酶（PKM2）的mRNA和蛋白水平，并降低有氧糖酵解能力。转染PKM2-siRNA可模拟AFC对结肠癌细胞有氧糖酵解的抑制作用。此外，还发现细胞中高表达的肿瘤特异性靶点c-myc和细胞周期蛋白D1在AFC作用后也下调。在HCT116细胞异种移植裸鼠模型中，给予AFC后的结果与细胞实验结果一致，而AFC比传统化疗药物5-氟尿嘧啶（5-FU）引起的肝损伤和体重减轻更小。总之，AFC通过下调PKM2来抑制有氧糖酵解，并降低c-myc和细胞周期蛋白D1的肿瘤特异性高表达，从而抑制结肠癌生长。未来的工作应首先探索其如何下调丙酮酸激酶（PK），以及PKM2下调与c-myc下调之间的内在机制。
