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Extrinsic nitric oxide donor partially reverses arginine deiminase induced cell growth inhibition through NFκB and Bcl-XL

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Summary

Arginine deiminase (ADI) is known to be an inducer of apoptosis in vitro and an anti-tumor agent in vivo in some cancers. ADI causes the enzymatic depletion of arginine which may inhibit nitric oxide (NO) synthesis. However, the effect of ADI treatment on NO synthesis has not been clearly elucidated. With the goal of understanding the role of ADI in NO synthesis, we used the Ramos human lymphoma cell line, which is known to be ADI-sensitive. After determining an optimal experimental ADI concentration (0.001 U/ml), we studied the effects of ADI treatment when combined with different concentrations of the extrinsic NO donor, sodium nitroprusside (SNP) (i.e., control, ADI only, ADI with 10 μM/ml SNP, ADI with 50 μM/ml SNP, and ADI with 100 μM/ml SNP). An MTT assay was used to assess cell survival after treatment, nitric oxide assays to determine nitrite levels and Western blot analysis to determine the expression of the NO mediators, NFκB and Bcl-X L . Interestingly, we found that the extrinsic NO donor only partially reversed ADI-induced inhibition of cell growth in a dose-dependent pattern and resulted in an induction of NFκB and Bcl-X L expression. In conclusion, we suggest that there might be an association between reversal of cell growth inhibition by extrinsic NO donor with Bcl-XL and NFκB expression in ADI-treated Ramos cell.

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Acknowledgements

This work was supported by grants from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PG3-PG6-01GN07-0004) and by The Post-Brain Korea 21 Project.

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea

    Jae Hong Seo, Hwa Jung Sung, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim & Jun Suk Kim

  2. Department of Pharmacology, College of Medicine, Korea University, Seoul, South Korea

    Bon Hong Min

  3. Section of Hematology and Oncology, Department of Internal Medicine, Korea University Guro Hospital, 97 Gurodong-gil, Guro-ku, Seoul, South Korea

    Jun Suk Kim

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  1. Jae Hong Seo
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Correspondence to Jun Suk Kim.

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Seo, J.H., Sung, H.J., Choi, C.W. et al. Extrinsic nitric oxide donor partially reverses arginine deiminase induced cell growth inhibition through NFκB and Bcl-XL . Invest New Drugs 26, 277–282 (2008). https://doi.org/10.1007/s10637-007-9105-0

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  • DOI: https://doi.org/10.1007/s10637-007-9105-0

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