Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis- diaminedichloroplatinum(II) in oral cancer cell lines

Yu Maki, Jun Murakami, Jun-Ichi Asaumi, Hidetsugu Tsujigiwa, Hitoshi Nagatsuka, Susumu Kokeguchi, Kazuhiro Fukui, Noriko Kawai, Yoshinobu Yanagi, Masahiro Kuroda, Noriaki Tanaka, Nagahide Matsubara, Kanji Kishi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) modulates the effectiveness of alkylating agents. However, the relationship between MGMT and the sensitivities to other agents has not been explored. In the present study, the association between MGMT expression and the cellular sensitivity to the platinum agent, CDDP was examined in four human oral cancer cell lines. CDDP depleted MGMT protein and mRNA levels in all four cell lines. Two cell lines with low MGMT expression were sensitive to an alkylating agent, N-methyl-N′-nitro-N-nitrosoguanidine and CDDP, whereas two other cell lines with high MGMT expression were resistant to both agents. Furthermore, the addition of the MGMT inhibitor, O6-benzylguanine (O 6-BG), invariably enhanced CDDP sensitivity. CDDP depleted MGMT expression, and CDDP sensitivity was enhanced by O6-BG. These results provide valuable information about the relationship between MGMT expression and CDDP sensitivity in oral cancer chemotherapy.

Original languageEnglish
Pages (from-to)984-993
Number of pages10
JournalOral Oncology
Volume41
Issue number10
DOIs
Publication statusPublished - Nov 2005

Fingerprint

Mouth Neoplasms
Methyltransferases
Cell Line
DNA
Neoplasms
Alkylating Agents
Protein Methyltransferases
DNA Repair Enzymes
O-(6)-methylguanine
O(6)-benzylguanine
Methylnitronitrosoguanidine
Platinum
Drug Therapy
Messenger RNA

Keywords

  • CDDP
  • MGMT
  • O-BG
  • Oral cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis- diaminedichloroplatinum(II) in oral cancer cell lines. / Maki, Yu; Murakami, Jun; Asaumi, Jun-Ichi; Tsujigiwa, Hidetsugu; Nagatsuka, Hitoshi; Kokeguchi, Susumu; Fukui, Kazuhiro; Kawai, Noriko; Yanagi, Yoshinobu; Kuroda, Masahiro; Tanaka, Noriaki; Matsubara, Nagahide; Kishi, Kanji.

In: Oral Oncology, Vol. 41, No. 10, 11.2005, p. 984-993.

Research output: Contribution to journalArticle

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