Induction of human leukemia HL-60 cell differentiation via a PKC/ERK pathway by helenalin, a pseudoguainolide sesquiterpene lactone.

Abstract

Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits nuclear factor-kappa B (NF-kappa B) DNA binding activity. In this report, we investigated the effect of helenalin on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Helenalin by itself markedly induced HL-60 cell differentiation in a concentration-dependent manner. Cytofluorometric analysis and cell morphologic studies indicated that helenalin induced cell differentiation predominantly into granulocytes. Protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors significantly inhibited HL-60 cell differentiation induced by helenalin, while p38 mitogen-activated protein kinase (MAPK) inhibitors did not. Moreover, helenalin enhanced PKC activity and protein level of PKC beta I and PKC beta II isoforms, and also increased the level of pERK in a concentration-dependent manner. In addition, the enhanced levels of cell differentiation closely correlated with the decreased levels of NF-kappa B binding activity by helenalin. These results indicate that PKC, ERK, and NF-kappa B may be involved in HL-60 cell differentiation induced by helenalin.

• Authors: Seung H Kim, Sang M Oh, Tae S Kim
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 511 Issue 2-3 Pg. 89-97 (Mar 28 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15792776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Androstadienes
• Antineoplastic Agents, Phytogenic
• Benzophenanthridines
• Chromones
• Enzyme Inhibitors
• Flavonoids
• Indoles
• Lactones
• Maleimides
• Morpholines
• NF-kappa B
• Phenanthridines
• Phosphoinositide-3 Kinase Inhibitors
• Sesquiterpenes
• Sesquiterpenes, Guaiane
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• helenalin
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• chelerythrine
• Protein Kinase C
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases
• bisindolylmaleimide I
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
• Wortmannin

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (pharmacology)
• Alkaloids
• Androstadienes (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Benzophenanthridines
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Flavonoids (pharmacology)
• HL-60 Cells
• Humans
• Indoles (pharmacology)
• Lactones (pharmacology)
• Maleimides (pharmacology)
• Models, Biological
• Morpholines (pharmacology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Phenanthridines (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Sesquiterpenes (pharmacology)
• Sesquiterpenes, Guaiane
• Signal Transduction (drug effects)
• Wortmannin
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)