ISSN: 1449-1907International Journal of Medical Sciences
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Int J Med Sci 2024; 21(5):904-913. doi:10.7150/ijms.93903 This issue Cite
Research Paper
Natural Product Quercetin-3-methyl ether Promotes Colorectal Cancer Cell Apoptosis by Downregulating Intracellular Polyamine Signaling
1. 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.
2. Department of Pathology, Binhaiwan Central Hospital of Dongguan, Dongguan 523000, China.
3. Dongguan Proof-of-Concept Centers for Medical Use, Guangdong Xinghai Institute of Cell, Dongguan 523808, China.
4. Department of Clinical Laboratory, Yuedong Hospital, The Third Affiliated Hospital of Sun Yat-sen University, China.
*These authors contributed equally.
Abstract
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.
Keywords: natural product, quercetin-3-methyl ether, colorectal cancer cell, cell apoptosis
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