Isodiospyrin as a novel human DNA topoisomerase I inhibitor

Chun Yuan Ting, Chia Tse Hsu, Hsiang Ting Hsu, Jin Shan Su, Tzong Yueh Chen, Woan Yuh Tarn, Yao Haur Kuo, Jacqueline Whang-Peng, Leroy F. Liu, Jaulang Hwang

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Isodiospyrin is a natural product from the plant Diospyros morrisiana, which consists of an asymmetrical 1,2-binaphthoquinone chromophore. Isodiospyrin exhibits cytotoxic activity to tumor cell lines but very little is known about its cellular target and mechanism of action. Unlike the prototypic human topoisomerase I (htopo I) poison camptothecin, isodiospyrin does not induce htopo I-DNA covalent complexes. However, isodiospyrin antagonizes camptothecin-induced, htopo I-mediated DNA cleavage. Binding analysis indicated that isodiospyrin binds htopo I but not DNA. These results suggest that isodiospyrin inhibits htopo I by direct binding to htopo I, which limits htopo I access to the DNA substrate. Furthermore, isodiospyrin exhibits strong inhibitory effect on the kinase activity of htopo I toward splicing factor 2/alternate splicing factor in the absence of DNA. Thus, these findings have important implications on naphthoquinone and its derivatives' cellular mode of actions, i.e. these novel DNA topoisomerase I inhibitors can prevent both DNA relaxation and kinase activities of htopo I.

Original languageEnglish
Pages (from-to)1981-1991
Number of pages11
JournalBiochemical Pharmacology
Volume66
Issue number10
DOIs
Publication statusPublished - Nov 15 2003
Externally publishedYes

Fingerprint

Topoisomerase I Inhibitors
Type I DNA Topoisomerase
Camptothecin
DNA
Diospyros
Polynucleotide 5'-Hydroxyl-Kinase
Naphthoquinones
DNA Cleavage
Poisons
Alternative Splicing
Chromophores
isodiospyrin
Tumor Cell Line
Biological Products
Human Activities
Tumors
Phosphotransferases
Cells
Derivatives
Substrates

Keywords

  • Binaphthoquinone
  • Camptothecin
  • Diospyros morrisiana
  • Human DNA topoisomerase I
  • Isodiospyrin
  • Kinase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ting, C. Y., Hsu, C. T., Hsu, H. T., Su, J. S., Chen, T. Y., Tarn, W. Y., ... Hwang, J. (2003). Isodiospyrin as a novel human DNA topoisomerase I inhibitor. Biochemical Pharmacology, 66(10), 1981-1991. https://doi.org/10.1016/j.bcp.2003.07.003

Isodiospyrin as a novel human DNA topoisomerase I inhibitor. / Ting, Chun Yuan; Hsu, Chia Tse; Hsu, Hsiang Ting; Su, Jin Shan; Chen, Tzong Yueh; Tarn, Woan Yuh; Kuo, Yao Haur; Whang-Peng, Jacqueline; Liu, Leroy F.; Hwang, Jaulang.

In: Biochemical Pharmacology, Vol. 66, No. 10, 15.11.2003, p. 1981-1991.

Research output: Contribution to journalArticle

Ting, CY, Hsu, CT, Hsu, HT, Su, JS, Chen, TY, Tarn, WY, Kuo, YH, Whang-Peng, J, Liu, LF & Hwang, J 2003, 'Isodiospyrin as a novel human DNA topoisomerase I inhibitor', Biochemical Pharmacology, vol. 66, no. 10, pp. 1981-1991. https://doi.org/10.1016/j.bcp.2003.07.003
Ting CY, Hsu CT, Hsu HT, Su JS, Chen TY, Tarn WY et al. Isodiospyrin as a novel human DNA topoisomerase I inhibitor. Biochemical Pharmacology. 2003 Nov 15;66(10):1981-1991. https://doi.org/10.1016/j.bcp.2003.07.003
Ting, Chun Yuan ; Hsu, Chia Tse ; Hsu, Hsiang Ting ; Su, Jin Shan ; Chen, Tzong Yueh ; Tarn, Woan Yuh ; Kuo, Yao Haur ; Whang-Peng, Jacqueline ; Liu, Leroy F. ; Hwang, Jaulang. / Isodiospyrin as a novel human DNA topoisomerase I inhibitor. In: Biochemical Pharmacology. 2003 ; Vol. 66, No. 10. pp. 1981-1991.
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