DNA-protein crosslinks are key to platinum-based chemotherapeutic cytotoxicity

DNA-protein crosslinks of platinum drugs

Authors

  • Mahmoud Shoulkamy Kanazawa University, Ishikawa, Japan https://orcid.org/0000-0002-4736-1212
  • Ming Zhang Xie First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
  • Cui-Li Jiao Bengbu Fourth People's Hospital, China
  • Tareg Omer Mohammed Kanazawa University, Ishikawa, Japan

DOI:

https://doi.org/10.62110/sciencein.cbl.2024.v11.663

Keywords:

Platinum-based chemotherapeutics, DNA damage, Interstrand crosslinks, Lethal Dose, protein damage, cancer therapeutics, cytotoxicity, DNA-protein crosslinks

Abstract

Platinum-based chemotherapeutics inflict a spectrum of DNA damage, including DNA adducts, DNA-protein crosslinks (DPCs), and interstrand crosslinks (ICLs) to variable extents. These diverse lesions may contribute to the overall toxicity of these therapeutic agents. Nonetheless, a gap exists in comparative studies elucidating the specific DNA damage responsible for their toxicity. Therefore, we exposed MRC5SV cells to equitoxic doses (LD10) of cisplatin (cisPt) and oxaliplatin (L-OHP) and systematically examined the induction of DPCs, ICL, and protein damage. Our findings suggest that DPCs emerge as the crucial cytotoxic DNA damage for both cisPt and L-OHP, highlighting their central role in the mechanism of action driving the cytotoxicity of platinum-based therapeutics. Both drugs show induction of ICLs as computed by the unique sensitivity of Fanconi anemia cells to the drugs. Additionally, both cisPt and L-OHP didn’t show protein damage as indicated by the absence of TRX1 oxidation post-treatment. Overall, our results underscore the critical involvement of DPCs in the toxicity of platinum-based drugs, emphasizing the importance of DPCs as potential cancer therapeutic targets.

URN:NBN:sciencein.cbl.2024.v11.663

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Author Biographies

  • Mahmoud Shoulkamy, Kanazawa University, Ishikawa, Japan

    WPI Nano Life Science Institute (WPI-Nano LSI)

  • Ming Zhang Xie, First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China

    Department of Genetics

  • Cui-Li Jiao, Bengbu Fourth People's Hospital, China

    Department of Radiology

  • Tareg Omer Mohammed, Kanazawa University, Ishikawa, Japan

    WPI Nano Life Science Institute (WPI-Nano LSI)

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Published

2024-04-04

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How to Cite

(1)
Shoulkamy, M.; Xie, M. Z. .; Jiao, C.-L. .; Mohammed, T. O. DNA-Protein Crosslinks Are Key to Platinum-Based Chemotherapeutic Cytotoxicity. Chem Biol Lett 2024, 11 (2), 663. https://doi.org/10.62110/sciencein.cbl.2024.v11.663.

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