Zeng Jincheng, Zhang Yuancheng, Fang Yuming, Lian Jiachun, Zhang Hailiang, Zhang Shaobing, Lin Bihua, Ye Ziyu, Li Caihong, Qiu Xianxiu, Liang Yanfang
Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
Dongguan Proof-of-Concept Centers for Medical Use, Guangdong Xinghai Institute of Cell, Dongguan 523808, China.
Int J Med Sci. 2024 Mar 25;21(5):904-913. doi: 10.7150/ijms.93903. eCollection 2024.
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.
细胞代谢失调是癌症的关键标志，有人提出应将代谢视为结直肠癌的一个靶向弱点。多胺代谢增加是肿瘤中常见的代谢变化。因此，针对多胺代谢进行抗癌治疗，尤其是多胺阻断治疗，已逐渐成为一个热门话题。槲皮素 - 3 - 甲醚是一种存在于多种植物中的天然化合物，具有抗氧化和抗衰老等多种生物活性。在此，我们报道槲皮素 - 3 - 甲醚以剂量和时间依赖性方式抑制结直肠癌细胞活力并促进细胞凋亡。有趣的是，用槲皮素 - 3 - 甲醚处理后，结直肠癌细胞中的多胺水平，包括亚精胺和精胺，会降低。这可能是由于多胺代谢中的关键酶SMOX（催化精胺氧化为亚精胺）表达下调所致。这些发现表明槲皮素 - 3 - 甲醚通过抑制SMOX表达降低细胞多胺水平，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 - 甲醚的药理活性以及它如何重新编程细胞多胺代谢提供新的见解。
