Tetra-O-methyl nordihydroguaiaretic acid induces G2 arrest in mammalian cells and exhibits tumoricidal activity in vivo

Jonathan D. Heller, Jennifer Kuo, T. C. Wu, W. Martin Kast, Ru Chih C. Huang

Research output: Contribution to journalArticle

Abstract

The transcription inhibitor tetra-O-methyl nordihydroguaiaretic acid (M4N) was found to arrest the proliferation of C3, C33a, CEM-T4, and TC-1 cells in culture at the G2 stage of the cell cycle. Investigation into the mechanism of arrest revealed that M4N reduces mRNA levels and subsequent protein production of the cyclin-dependent kinase CDC2, resulting in the inactivation of the CDC2/cyclin B complex (maturation promoting factor). When injected intratumorally in a C3-cell induced C57b1/6 mouse tumor model system, M4N demonstrated substantial tumoricidal activity that correlated with a reduction in tumor cell CDC2 protein levels. These findings suggest that M4N may be a useful chemotherapeutic agent for the control of unregulated cellular proliferation.

Original languageEnglish (US)
Pages (from-to)5499-5504
Number of pages6
JournalCancer Research
Volume61
Issue number14
StatePublished - Jul 15 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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