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09.01.2024 | Original Article

Ruthenium–dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation

verfasst von: Chong-Zhi Wang, Chunping Wan, Cang-Hai Li, Guo-Gang Liang, Yun Luo, Chun-Feng Zhang, Qi-Hui Zhang, Qinge Ma, Angela H. Wang, Mallory Lager, Ting-Liang Jiang, Lifei Hou, Chun-Su Yuan

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2024

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Abstract

Background

Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies.

Methods

To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium–dihydroartemisinin complex (D–Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties.

Results

Compared with its parent compound, ART, D–Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D–Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D–Ru downregulated the expressions of pro-inflammatory cytokines IL-1β, IL-6, and IL-8. Although ART and D–Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation.

Conclusions

Our results demonstrated that D–Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound’s anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D–Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

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Titel: Ruthenium–dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation
verfasst von: Chong-Zhi Wang
Chunping Wan
Cang-Hai Li
Guo-Gang Liang
Yun Luo
Chun-Feng Zhang
Qi-Hui Zhang
Qinge Ma
Angela H. Wang
Mallory Lager
Ting-Liang Jiang
Lifei Hou
Chun-Su Yuan
Publikationsdatum: 09.01.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2024
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-023-04623-7

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Ruthenium–dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation