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Hint from an Enzymatic Reaction: Superoxide Dismutase Models Efficiently Suppress Colorectal Cancer Cell
Hanae Lim1, Chaeun Oh2, Myong-Suk Park3
1Department of Chemistry, Sookmyung Women's University, Seoul 04310, Korea.
Abstract:
Superoxide dismutases (SODs) are essential antioxidant enzymes that prevent massive superoxide radical production and thus protect cells from damage induced by free radicals. However, this concept has rarely been applied to directly impede the function of driver oncogenes, thus far. Here, leveraging efforts from SOD model complexes, we report the novel finding of biomimetic copper complexes that efficiently scavenge intracellularly generated free radicals and, thereby, directly access the core consequence of colorectal cancer suppression. We conceived four structurally different SOD-mimicking copper complexes that showed distinct disproportionation reaction rates of intracellular superoxide radical anions. By replenishing SOD models, we observed a dramatic reduction of intracellular reactive oxygen species (ROS) and adenine 5'-triphosphate (ATP) concentrations that led to cell cycle arrest at the G2/M stage and induced apoptosis in vitro and in vivo. Our results showcase how nature-mimicking models can be designed and fine-tuned to serve as a viable chemotherapeutic strategy for cancer treatment.
Insights
Novel biomimetic copper complexes mimic superoxide dismutases (SODs) to scavenge free radicals. This approach effectively reduces reactive oxygen species (ROS), inhibiting colorectal cancer progression and offering a new chemotherapeutic strategy.
Area of Science:
- Biomimetic chemistry
- Antioxidant enzyme mimetics
- Cancer therapy
Background:
- Superoxide dismutases (SODs) are crucial antioxidant enzymes protecting cells from free radical damage.
- The therapeutic potential of SOD mimetics for directly targeting oncogenes remains underexplored.
- Reactive oxygen species (ROS) play a significant role in cancer progression, including colorectal cancer.
Purpose of the Study:
- To design and synthesize novel biomimetic copper complexes that mimic SOD activity.
- To investigate the efficacy of these complexes in scavenging intracellular free radicals.
- To evaluate their potential as a chemotherapeutic strategy for colorectal cancer.
Main Methods:
- Synthesis of four structurally distinct SOD-mimicking copper complexes.
- Assessment of their superoxide radical anion disproportionation rates.
- In vitro and in vivo evaluation of their effects on intracellular ROS and ATP levels, cell cycle, and apoptosis.
Main Results:
- The designed copper complexes efficiently scavenged intracellular superoxide radicals.
- A significant reduction in intracellular ROS and ATP concentrations was observed.
- These complexes induced G2/M cell cycle arrest and apoptosis in cancer cells, both in vitro and in vivo.
Conclusions:
- Biomimetic copper complexes can effectively mimic SOD activity to reduce intracellular oxidative stress.
- This strategy directly impacts colorectal cancer progression by inducing cell cycle arrest and apoptosis.
- Nature-mimicking SOD models offer a promising avenue for developing novel cancer chemotherapeutics.
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