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Article

Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway

  • Authors:
    • Koji Nishi
    • Yoshifumi Arimura
    • Naho Suetsugi
    • Takuro Beppu
    • Kaho Takasaki
    • Ayano Tamori
    • Ryo Kanda
    • Shuhei Imoto
    • Hirotaka Murase
    • Kenji Tsukigawa
    • Masaki Otagiri
    • Keishi Yamasaki
  • View Affiliations / Copyright

    Affiliations: Faculty of Pharmaceutical Sciences, Sojo University, Nishi‑ku, Kumamoto 860‑0082, Japan
  • Article Number: 159
    |
    Published online on: August 29, 2024
       https://doi.org/10.3892/br.2024.1847
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Abstract

Nitric oxide (NO) has been reported to have a cytotoxic effect on various types of cancer. However, the efficient delivery of NO donors to tumors remains challenging. The present study used ibuprofen, which has a high binding affinity to human serum albumin (HSA). A total of two types of nitrated forms of ibuprofen, 4‑[(nitrooxy)methyl]benzyl 2‑(4‑isobutylphenyl)propanoate [nitrated ibuprofen benzyl linker (NIB)] and 2‑(nitrooxy)ethyl 2‑(4‑isobutylphenyl) propanoate [nitrated ibuprofen ethyl linker (NIE)], were synthesized. It was demonstrated that both NIB and NIE bound to the ibuprofen‑binding site of HSA. Although NOx release was observed from NIB, but not NIE, intracellular NO release was detected from both NIB and NIE, which indicated that the mechanisms of NO release may be different for NIB and NIE. Both NIB and NIE induced concentration‑ and time‑dependent cell death in human pancreatic cancer cells, whereas this cell death was not observed with ibuprofen, which could suggest that these cell death‑inducing effects may be mediated by NO. The non‑specific caspase inhibitor, z‑VAD‑FMK, inhibited cell death induced by NIB and NIE, but activation of caspase 3/7 was not observed. These results suggested that both NIB and NIE induced cell death through a non‑caspase 3/7 pathway. The findings of the present study demonstrated that both NIB and NIE, as NO donors that could be retained in blood, may potentially be useful anti‑cancer agent candidates in the future.
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Copy and paste a formatted citation
Spandidos Publications style
Nishi K, Arimura Y, Suetsugi N, Beppu T, Takasaki K, Tamori A, Kanda R, Imoto S, Murase H, Tsukigawa K, Tsukigawa K, et al: Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway. Biomed Rep 21: 159, 2024.
APA
Nishi, K., Arimura, Y., Suetsugi, N., Beppu, T., Takasaki, K., Tamori, A. ... Yamasaki, K. (2024). Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway. Biomedical Reports, 21, 159. https://doi.org/10.3892/br.2024.1847
MLA
Nishi, K., Arimura, Y., Suetsugi, N., Beppu, T., Takasaki, K., Tamori, A., Kanda, R., Imoto, S., Murase, H., Tsukigawa, K., Otagiri, M., Yamasaki, K."Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway". Biomedical Reports 21.5 (2024): 159.
Chicago
Nishi, K., Arimura, Y., Suetsugi, N., Beppu, T., Takasaki, K., Tamori, A., Kanda, R., Imoto, S., Murase, H., Tsukigawa, K., Otagiri, M., Yamasaki, K."Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway". Biomedical Reports 21, no. 5 (2024): 159. https://doi.org/10.3892/br.2024.1847
Copy and paste a formatted citation
x
Spandidos Publications style
Nishi K, Arimura Y, Suetsugi N, Beppu T, Takasaki K, Tamori A, Kanda R, Imoto S, Murase H, Tsukigawa K, Tsukigawa K, et al: Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway. Biomed Rep 21: 159, 2024.
APA
Nishi, K., Arimura, Y., Suetsugi, N., Beppu, T., Takasaki, K., Tamori, A. ... Yamasaki, K. (2024). Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway. Biomedical Reports, 21, 159. https://doi.org/10.3892/br.2024.1847
MLA
Nishi, K., Arimura, Y., Suetsugi, N., Beppu, T., Takasaki, K., Tamori, A., Kanda, R., Imoto, S., Murase, H., Tsukigawa, K., Otagiri, M., Yamasaki, K."Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway". Biomedical Reports 21.5 (2024): 159.
Chicago
Nishi, K., Arimura, Y., Suetsugi, N., Beppu, T., Takasaki, K., Tamori, A., Kanda, R., Imoto, S., Murase, H., Tsukigawa, K., Otagiri, M., Yamasaki, K."Ibuprofen‑derived nitric oxide donors with a high affinity to human serum albumin induce cell death in pancreatic cancer cells through a non‑caspase 3/7‑mediated pathway". Biomedical Reports 21, no. 5 (2024): 159. https://doi.org/10.3892/br.2024.1847
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