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NF-kappaB pathway is involved in griseofulvin-induced G2/M arrest and apoptosis in HL-60 cells

Yih-Huei Uen1, Der-Zen Liu, Meng-Shih Weng

  • 1Department of Surgery, Chi-Mei Foundational Medical Center, Yung-Kang City, Tainan, Taiwan.

Journal of Cellular Biochemistry
|January 18, 2007
PubMed

Insights

Griseofulvin induces G2/M cell cycle arrest and apoptosis in HL-60 cells, involving NF-kappaB and JNK pathways. This antifungal agent

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Pharmacology

Background:

  • Griseofulvin (GF), an antifungal, shows potential antitumor effects via G2/M cell cycle arrest in colon cancer.
  • The precise molecular mechanisms underlying GF's anticancer activity remain unclear.

Purpose of the Study:

  • To investigate the cytotoxic effects of Griseofulvin on HL-60 and HT-29 cancer cell lines.
  • To elucidate the molecular pathways mediating Griseofulvin's effects on cell cycle progression and apoptosis.

Main Methods:

  • Flow cytometry was used for dose-dependent and time-course analyses of cell cycle arrest and apoptosis.
  • Electrophoretic mobility shift assay (EMSA) and super-shift analysis assessed NF-kappaB binding activity.
  • Western blotting and kinase assays evaluated the activation of JNK, ERK, p38 MAPK, and cdc-2 kinase, as well as Bcl-2 phosphorylation.

Main Results:

  • Griseofulvin (30-60 microM) induced significant G2/M arrest and apoptosis in HL-60 cells, and G2/M arrest in HT-29 cells.
  • TPCK, a serine protease inhibitor, reversed GF-induced G2/M arrest and apoptosis in HL-60 cells but not HT-29 cells.
  • GF activated NF-kappaB binding activity and JNK, leading to Bcl-2 phosphorylation and cdc-2 kinase activation in HL-60 cells, which was partially inhibited by TPCK.

Conclusions:

  • Griseofulvin-induced G2/M cell cycle arrest in HL-60 cells is mediated by NF-kappaB activation, JNK signaling, and subsequent Bcl-2 phosphorylation and cdc-2 kinase activation.
  • The findings suggest distinct mechanisms of action for Griseofulvin in different cancer cell types.
  • Griseofulvin's potential as an anticancer agent warrants further investigation into its molecular targets.

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