Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells

  • Authors:
    • Takuya Ohta
    • Hiroki Hori
    • Masahiro Ogawa
    • Masazumi Miyahara
    • Hajime Kawasaki
    • Norihisa Taniguchi
    • Yoshihiro Komada
  • View Affiliations

  • Published online on: November 1, 2004     https://doi.org/10.3892/or.12.5.1115
  • Pages: 1115-1120
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Abstract

Cytarabine (araC) is a highly active antimetabolite against hematological malignancy while the agent shows limited activity against carcinomas. In this study, we focused on cellular transport and catalysis of the nucleoside in order to elucidate the mechanism of intrinsic resistance to araC in carcinomas. Activities of two metabolizing enzymes for araC, deoxycytidine kinase (DCK) and cytidine deaminase (CDA), and cellular transport of the agent were examined in 9 carcinoma cell lines. These variables in carcinoma lines were compared with those in 14 araC-sensitive leukemia lines and one leukemia line with acquired resistance. The mean IC50 in 9 carcinoma lines was 3x103-fold higher than that in 14 leukemia lines (4.6x103 vs. 1.3 µM, p<0.01). A cell line with acquired resistance (U937R), which was established from U937 monocytoid leukemia cells, showed more than 103-fold higher IC50 than the parent cells (1.6x103 vs. 1.3 µM). The resistance in carcinomas was associated with higher CDA activity and lower influx when compared to araC sensitive leukemias. Especially, these two types of malignant cell lines were clearly distinguished by CDA activity. The acquired resistance in U937R cells was followed by increase in cytidine deaminase (CDA) activity, decrease in DCK activity and decrease in influx of the drug. In conclusion, carcinomas are intrinsically resistant to cytarabine through high CDA activity and low cellular transport, but not low DCK activity. This finding suggests that treatment of carcinoma with deoxycytidine analogues should conquer the high CDA activity.

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November 2004
Volume 12 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ohta T, Hori H, Ogawa M, Miyahara M, Kawasaki H, Taniguchi N and Komada Y: Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells. Oncol Rep 12: 1115-1120, 2004
APA
Ohta, T., Hori, H., Ogawa, M., Miyahara, M., Kawasaki, H., Taniguchi, N., & Komada, Y. (2004). Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells. Oncology Reports, 12, 1115-1120. https://doi.org/10.3892/or.12.5.1115
MLA
Ohta, T., Hori, H., Ogawa, M., Miyahara, M., Kawasaki, H., Taniguchi, N., Komada, Y."Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells". Oncology Reports 12.5 (2004): 1115-1120.
Chicago
Ohta, T., Hori, H., Ogawa, M., Miyahara, M., Kawasaki, H., Taniguchi, N., Komada, Y."Impact of cytidine deaminase activity on intrinsic resistance to cytarabine in carcinoma cells". Oncology Reports 12, no. 5 (2004): 1115-1120. https://doi.org/10.3892/or.12.5.1115