(-)-Neocaryachine, an antiproliferative pavine alkaloid from Cryptocarya laevigata, induces DNA double-strand breaks

Yuki Suzuki, Yohei Saito, Masuo Goto, David J. Newman, Barry R. O'Keefe, Kuo Hsiung Lee, Kyoko Nakagawa-Goto

Research output: Research - peer-reviewArticle

Abstract

Twelve benzylisoquinoline alkaloids, including pavine and phenanthroindolizidine types, were isolated from a MeOH/CH2Cl2 extract of Cryptocarya laevigata (stem bark) through bioactivity-guided fractionation for antitumor effects. Selected compounds were evaluated for antiproliferative activity against five human tumor cell lines, including a multidrug-resistant subline. Since more common 2,3,8,9-tetrasubstituted pavine alkaloids, such as crychine (3), exhibit very mild or no cytotoxicity, this compound type has not been well investigated for antitumor activity. Thus, this report is the first discovery of a 7-hydroxylated pavine alkaloid, (-)-neocaryachine (1), to demonstrate strong antiproliferative activity, with IC50 values of 0.06 to 0.41 μM against five tested tumor cell lines, including an MDR subline. Further mechanism of action studies revealed that 1 impacts the cellular S-phase by inducing DNA double-strand breaks. (Figure Presented).

LanguageEnglish (US)
Pages220-224
Number of pages5
JournalJournal of Natural Products
Volume80
Issue number1
DOIs
StatePublished - Jan 27 2017

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Alkaloids
DNA
Cryptocarya
Double-Stranded DNA Breaks
Tumors
Cells
Tumor Cell Line
Benzylisoquinolines
Cytotoxicity
Fractionation
Bioactivity
phenanthroindolizidine
crychine
S Phase

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

(-)-Neocaryachine, an antiproliferative pavine alkaloid from Cryptocarya laevigata, induces DNA double-strand breaks. / Suzuki, Yuki; Saito, Yohei; Goto, Masuo; Newman, David J.; O'Keefe, Barry R.; Lee, Kuo Hsiung; Nakagawa-Goto, Kyoko.

In: Journal of Natural Products, Vol. 80, No. 1, 27.01.2017, p. 220-224.

Research output: Research - peer-reviewArticle

Suzuki, Yuki ; Saito, Yohei ; Goto, Masuo ; Newman, David J. ; O'Keefe, Barry R. ; Lee, Kuo Hsiung ; Nakagawa-Goto, Kyoko. / (-)-Neocaryachine, an antiproliferative pavine alkaloid from Cryptocarya laevigata, induces DNA double-strand breaks. In: Journal of Natural Products. 2017 ; Vol. 80, No. 1. pp. 220-224
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