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Tyrphostin induces non‐apoptotic programmed cell death in colon tumor cells
Author(s) -
Szende B.,
Kéri Gy.,
Szegedi Zs.,
Benedeczky I.,
Csikós A.,
Örfi L.,
Gazit A.
Publication year - 1995
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1006/cbir.1995.1028
Subject(s) - programmed cell death , cycloheximide , apoptosis , biology , tyrosine kinase , microbiology and biotechnology , protein tyrosine phosphatase , receptor tyrosine kinase , cancer research , tyrosine kinase inhibitor , kinase , signal transduction , biochemistry , cancer , protein biosynthesis , genetics
Abstract The programmed cell death inducing effect of the EGF receptor tyrosine kinase inhibitor α‐cyano‐3,4‐dihydroxycinnamthioamide (AG213) was investigated in vitro on HT‐29 human colon tumor. AG213 at concentrations between 45 to 450 μM 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.