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Natural Product Quercetin-3-methyl ether Promotes Colorectal Cancer Cell Apoptosis by Downregulating Intracellular
Jincheng Zeng1, Yuancheng Zhang1,2, Yuming Fang1,3,4
1Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China.
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.
Insights
Quercetin-3-methyl ether, a natural compound, effectively reduces colorectal cancer cell viability and promotes apoptosis. It achieves this by lowering polyamine levels through the suppression of SMOX, a key metabolic enzyme.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Cellular metabolism dysregulation is a hallmark of cancer, presenting a potential therapeutic vulnerability.
- Elevated polyamine metabolism is frequently observed in tumors, making it a target for anticancer strategies.
- Polyamines are crucial for cell growth and proliferation, and their dysregulation is linked to cancer development.
Purpose of the Study:
- To investigate the effects of Quercetin-3-methyl ether on colorectal cancer cell viability and apoptosis.
- To explore the impact of Quercetin-3-methyl ether on polyamine metabolism in colorectal cancer cells.
- To elucidate the underlying molecular mechanisms of Quercetin-3-methyl ether's anti-cancer activity.
Main Methods:
- Cell viability assays to assess the effect of Quercetin-3-methyl ether on colorectal cancer cell proliferation.
- Apoptosis assays to quantify the induction of programmed cell death.
- Measurement of intracellular polyamine levels (spermidine, spermine) and analysis of SMOX enzyme expression.
Main Results:
- Quercetin-3-methyl ether significantly inhibited colorectal cancer cell viability and induced apoptosis in a dose- and time-dependent manner.
- Treatment with Quercetin-3-methyl ether led to a reduction in cellular spermidine and spermine levels.
- The compound downregulated the expression of SMOX (spermine oxidase), a key enzyme in polyamine catabolism.
Conclusions:
- Quercetin-3-methyl ether exhibits anti-cancer properties against colorectal cancer by modulating polyamine metabolism.
- Suppression of SMOX expression by Quercetin-3-methyl ether leads to decreased polyamine levels and subsequent apoptosis.
- These findings highlight the potential of Quercetin-3-methyl ether as a therapeutic agent and offer insights into its mechanism of action in cancer treatment.
