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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)716-723
Number of pages8
JournalCancer Science
Volume97
Issue number8
DOIs
Publication statusPublished - Aug 1 2006

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Type II DNA Topoisomerase
Ubiquinone
DNA-Directed DNA Polymerase
Terpenes
Cell Line
coenzyme Q10
Lethal Dose 50
Growth
Inhibitory Concentration 50
Neoplasms
HIV Reverse Transcriptase
DNA Polymerase I
Quinine
HL-60 Cells
Deoxyribonuclease I
G1 Phase
Electron Transport
Eukaryota
S Phase
DNA Repair

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Inhibitory effect of coenzyme Q1 on eukaryotic DNA polymerase γ and DNA topoisomerase II activities on the growth of a human cancer cell line. / Yonezawa, Yuko; Kuriyama, Isoko; Fukuoh, Atsushi; Muta, Tsuyoshi; Kang, Dongchon; Takemura, Masaharu; Kato, Ikuo; Yoshida, Hiromi; Mizushina, Yoshiyuki.

In: Cancer Science, Vol. 97, No. 8, 01.08.2006, p. 716-723.

Research output: Contribution to journalArticle

Yonezawa, Yuko ; Kuriyama, Isoko ; Fukuoh, Atsushi ; Muta, Tsuyoshi ; Kang, Dongchon ; Takemura, Masaharu ; Kato, Ikuo ; Yoshida, Hiromi ; Mizushina, Yoshiyuki. / Inhibitory effect of coenzyme Q1 on eukaryotic DNA polymerase γ and DNA topoisomerase II activities on the growth of a human cancer cell line. In: Cancer Science. 2006 ; Vol. 97, No. 8. pp. 716-723.
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AU - Muta, Tsuyoshi

AU - Kang, Dongchon

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AU - Kato, Ikuo

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AU - Mizushina, Yoshiyuki

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N2 - 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.

AB - 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.

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