Hint from an Enzymatic Reaction: Superoxide Dismutase Models Efficiently Suppress Colorectal Cancer Cell Proliferation

Hanae Lim, Chaeun Oh, Myong Suk Park, Hyung Bin Park, Chaewon Ahn, Woo Kyun Bae, Kyung Hyun Yoo, Seungwoo Hong

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Pages (from-to)16058-16068
Number of pages11
JournalJournal of the American Chemical Society
Volume145
Issue number29
DOIs
StatePublished - 26 Jul 2023

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

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