Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.

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天然产物槲皮素-3-甲醚通过下调细胞内多胺信号传导促进结直肠癌细胞凋亡

细胞代谢失调是癌症的一个关键标志，建议将代谢视为结直肠癌的目标弱点。多胺代谢增加是肿瘤中常见的代谢变化。因此，针对多胺代谢的抗癌治疗，特别是多胺阻断治疗逐渐成为研究热点。 3-甲基槲皮素是存在于多种植物中的天然化合物，具有抗氧化、抗衰老等多种生物活性。在这里，我们报道了槲皮素-3-甲基醚抑制结直肠癌细胞的活力，并以剂量​​依赖性和时间依赖性的方式促进细胞凋亡。有趣的是，经过槲皮素-3-甲基醚处理后，结直肠癌细胞中的多胺水平（包括亚精胺和精胺）降低了。这可能是由于 SMOX 下调所致，SMOX 是多胺代谢中的关键酶，可催化精胺氧化为亚精胺。这些发现表明槲皮素-3-甲醚通过抑制 SMOX 表达来降低细胞多胺水平，从而诱导结直肠癌细胞凋亡。我们的结果还揭示了槲皮素-3-甲基醚的抗肿瘤活性与多胺代谢调节之间的相关性，这可能为更好地理解槲皮素-3-甲基醚的药理活性及其如何重新编程细胞提供新的见解。多胺代谢。