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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1951-1960
Number of pages10
JournalInternational journal of oncology
Volume42
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

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Ribonucleotide Reductases
Esophageal Neoplasms
Fluorouracil
DNA Damage
Cell Line
Metabolic Networks and Pathways
Cisplatin
DNA
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Involvement of ribonucleotide reductase-M1 in 5-fluorouracil.-induced DNA damage in esophageal cancer cell lines. / Aoki, Yoshiro; Sakogawa, Kenji; Hihara, Jun; Emi, Manabu; Hamai, Yoichi; Kono, Kazuteru; Shi, Lin; Sun, Jiying; Kitao, Hiroyuki; Ikura, Tsuyoshi; Niida, Hiroyuki; Nakanishi, Makoto; Okada, Morihito; Tashiro, Satoshi.

In: International journal of oncology, Vol. 42, No. 6, 01.06.2013, p. 1951-1960.

Research output: Contribution to journalArticle

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 2013, 'Involvement of ribonucleotide reductase-M1 in 5-fluorouracil.-induced DNA damage in esophageal cancer cell lines', International journal of oncology, vol. 42, no. 6, pp. 1951-1960. https://doi.org/10.3892/ijo.2013.1899
Aoki, Yoshiro ; Sakogawa, Kenji ; Hihara, Jun ; Emi, Manabu ; Hamai, Yoichi ; Kono, Kazuteru ; Shi, Lin ; Sun, Jiying ; Kitao, Hiroyuki ; Ikura, Tsuyoshi ; Niida, Hiroyuki ; Nakanishi, Makoto ; Okada, Morihito ; Tashiro, Satoshi. / Involvement of ribonucleotide reductase-M1 in 5-fluorouracil.-induced DNA damage in esophageal cancer cell lines. In: International journal of oncology. 2013 ; Vol. 42, No. 6. pp. 1951-1960.
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