Tyrphostin induces non-apoptotic programmed cell death in colon tumor cells.

Abstract

The programmed cell death inducing effect of the EGF receptor tyrosine kinase inhibitor alpha-cyano-3,4-dihydroxycinnamthioamide (AG213) was investigated in vitro on HT-29 human colon tumor. AG213 at concentrations between 45 to 450 microM blocks the proliferation of HT-29 cells. Morphological findings suggest that the selective tyrosine kinase inhibitor AG213 induces Clarke III type (non-lysosomal vesiculate cytoplasmic) programmed cell death; unlike ATP analog non-selective tyrosine kinase inhibitors like Genistein which were found to induce apoptosis. Cycloheximide and Actinomycin-D reduced the effect of AG213 pointing to the fact that protein and RNA synthesis are also needed for this form of cell death. Acid phosphatase activity was found in the Golgi and in the newly formed intracytoplasmic vacuoles 3 hours after AG213 treatment which disappeared by 6 hours. The induction of Clarke III cell death by tyrosine kinase inhibitors may open a new modality to selective killing of tumor cells.

• Authors: B Szende, G Kéri, Z Szegedi, I Benedeczky, A Csikós, L Orfi, A Gazit
• Journal: Cell biology international (Cell Biol Int) Vol. 19 Issue 11 Pg. 903-11 (Nov 1995) ISSN: 1065-6995 [Print] England
• PMID: 8574217 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catechols
• Enzyme Inhibitors
• Nitriles
• Tyrphostins
• tyrphostin 47
• Dactinomycin
• Cycloheximide
• ErbB Receptors
• Protein-Tyrosine Kinases
• Acid Phosphatase

Topics

• Acid Phosphatase (metabolism)
• Apoptosis (drug effects)
• Catechols (pharmacology)
• Cell Count
• Cell Survival (drug effects)
• Cycloheximide (pharmacology)
• Dactinomycin (pharmacology)
• Enzyme Inhibitors (pharmacology)
• ErbB Receptors (metabolism)
• HT29 Cells (cytology, enzymology, ultrastructure)
• Humans
• Nitriles (pharmacology)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Tyrphostins