Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines

  • Authors:
    • Yoshiro Aoki
    • Kenji Sakogawa
    • Jun Hihara
    • Manabu Emi
    • Yoichi Hamai
    • Kazuteru Kono
    • Lin Shi
    • Jiying Sun
    • Hiroyuki Kitao
    • Tsuyoshi Ikura
    • Hiroyuki Niida
    • Makoto Nakanishi
    • Morihito Okada
    • Satoshi Tashiro
  • View Affiliations

  • Published online on: April 16, 2013     https://doi.org/10.3892/ijo.2013.1899
  • Pages: 1951-1960
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Abstract

5-Fluorouracil (5-FU) is one of the most well established chemotherapeutic agents in the treatment of esophageal cancer. Ribonucleotide reductase M1 (RRM-1) is the rate‑limiting enzyme in de novo DNA synthesis, and has been considered to play an important role in the 5-FU metabolic pathway. However, the means by which RRM-1 participates in the anticancer effects of 5-FU and cisplatin (CDDP) have not been well studied. Here, we show that RRM-1 significantly contributes to the induction of DNA damage by 5-FU in esophageal cancer cell lines. An assay of γ-H2AX focus formation, a marker of DNA damage, after 5-FU treatment revealed good correlation with the levels of RRM-1 protein expression. Moreover, the increased sensitivity and RAD51 focus formation induced by the combination treatment of 5-FU and CDDP were significantly repressed by RRM-1 depletion. These results suggest that RRM-1 is involved not only in the induction of DNA damage by 5-FU but also in the synergistic cytotoxic effect in the combination therapy of 5-FU and CDDP.
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June 2013
Volume 42 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K. ... Tashiro, S. (2013). Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines. International Journal of Oncology, 42, 1951-1960. https://doi.org/10.3892/ijo.2013.1899
MLA
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K., Shi, L., Sun, J., Kitao, H., Ikura, T., Niida, H., Nakanishi, M., Okada, M., Tashiro, S."Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines". International Journal of Oncology 42.6 (2013): 1951-1960.
Chicago
Aoki, Y., Sakogawa, K., Hihara, J., Emi, M., Hamai, Y., Kono, K., Shi, L., Sun, J., Kitao, H., Ikura, T., Niida, H., Nakanishi, M., Okada, M., Tashiro, S."Involvement of ribonucleotide reductase-M1 in 5-fluorouracil‑induced DNA damage in esophageal cancer cell lines". International Journal of Oncology 42, no. 6 (2013): 1951-1960. https://doi.org/10.3892/ijo.2013.1899