A glutathione S-transferase inducer from papaya: Rapid screening, identification and structure-activity relationship of isothiocyanates

Yoshimasa Nakamura, Yasujiro Morimitsu, Tomoko Uzu, Hajime Ohigashi, Akira Murakami, Yuko Naito, Yoko Nakagawa, Toshihiko Osawa, Koji Uchida

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We have developed a simple system for rapid detection and measurement of glutathione S-transferase placental form (GSTP1) that detoxify polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, (RL34) cells. Survey of fruit extracts for GST inducing ability identified both papaya and avocado as significant sources. Benzyl isothiocyanate (BITC) was isolated from papaya methanol extract as a principal inducer of GST activity. Further, the GST inducing ability of a total of 20 isothiocyanates (ITCs) and their derivatives was investigated. Some ITCs showed significant induction, and BITC was one of the most potent inducers among all compounds tested in the present study. The modification of isothiocyanate group (-NCS) or introduction of substituent group to the α- carbon modifies GST induction. Moreover, a significant correlation (P <0.01, r = 0.913) between the GST activity enrichment and GSTP1 protein induction by ITCs was observed. We also indicated that phenethyl ITC and nitrophenyl ITC, potently inducing GST activity, but not inactive benzyl isocyanate, are potential inducers of intracellular reactive oxygen intermediates (ROIs). Our system of GSTP1 induction is appropriate for the chemical research such as screening and identification of novel type of inducers as well as the structure-activity relationship studies, providing mechanistic insight into essential structural elements for GSTP1 induction. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)193-200
Number of pages8
JournalCancer Letters
Volume157
Issue number2
DOIs
Publication statusPublished - Sep 1 2000
Externally publishedYes

Fingerprint

Isothiocyanates
Carica
Structure-Activity Relationship
Glutathione Transferase
Persea
Isocyanates
Polycyclic Aromatic Hydrocarbons
Methanol
Fruit
Carbon
Epithelial Cells
Oxygen
Cell Line
Liver
Research
Proteins
benzyl isothiocyanate

Keywords

  • Fruit
  • Glutathione S-transferase
  • Isothiocyanate
  • Papaya
  • Rat normal liver epithelial cell line

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

A glutathione S-transferase inducer from papaya : Rapid screening, identification and structure-activity relationship of isothiocyanates. / Nakamura, Yoshimasa; Morimitsu, Yasujiro; Uzu, Tomoko; Ohigashi, Hajime; Murakami, Akira; Naito, Yuko; Nakagawa, Yoko; Osawa, Toshihiko; Uchida, Koji.

In: Cancer Letters, Vol. 157, No. 2, 01.09.2000, p. 193-200.

Research output: Contribution to journalArticle

Nakamura, Yoshimasa ; Morimitsu, Yasujiro ; Uzu, Tomoko ; Ohigashi, Hajime ; Murakami, Akira ; Naito, Yuko ; Nakagawa, Yoko ; Osawa, Toshihiko ; Uchida, Koji. / A glutathione S-transferase inducer from papaya : Rapid screening, identification and structure-activity relationship of isothiocyanates. In: Cancer Letters. 2000 ; Vol. 157, No. 2. pp. 193-200.
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