Inhibitory effect of coenzyme Q1 on eukaryotic DNA polymerase γ and DNA topoisomerase II activities on the growth of a human cancer cell line

Yuko Yonezawa, Isoko Kuriyama, Atsushi Fukuoh, Tsuyoshi Muta, Dongchon Kang, Masaharu Takemura, Ikuo Kato, Hiromi Yoshida, Yoshiyuki Mizushina

研究成果: ジャーナルへの寄稿学術誌査読

14 被引用数 (Scopus)

抄録

Coenzyme Q (CoQ) is an isoprenoid quinine that functions as an electron carrier in the mitochondrial respiratory chain in eukaryotes. CoQ having shorter isoprenoid chains, especially CoQ1 and CoQ2, selectively inhibited the in vitro activity of eukaryotic DNA polymerase (pol) γ, which is a mitochondrial pol. These compounds did not influence the activities of nuclear DNA replicative pols such as α, δ and ε, and nuclear DNA repair-related pols such as β, η, ι, κ and λ. CoQ also inhibited DNA topoisomerase II (topo II) activity, although the enzymatic characteristics, including modes of action, amino acid sequences and three-dimensional structures, were markedly different from those of pol γ. These compounds did not inhibit the activities of procaryotic pols such as Escherichia coli pol I, and other DNA metabolic enzymes such as human immunodeficiency virus reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. CoQ1, which has the shortest isoprenoid chains, had the strongest inhibitory effect on pol γ and topo II activities among CoQ1-CoQ10, with 50% inhibitory concentration (IC50) values of 12.2 and 15.5 μM, respectively. CoQ1 could prevent the growth of human promyelocytic leukemia cells, HL-60, and the 50% lethal dose (LD50) value was 14.0 μM. The cells were halted at S phase and G1 phase in the cell cycle, and suppressed mitochondrial proliferation. From these results, the relationship between the inhibition of pol γ/topo II and cancer cell growth by CoQ is discussed.

本文言語英語
ページ(範囲)716-723
ページ数8
ジャーナルCancer Science
97
8
DOI
出版ステータス出版済み - 8月 2006

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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