Role of protein tyrosine phosphorylation in etoposide-induced apoptosis and NF-kappa B activation

Biochemical Pharmacology
I UsamiK Furusho

Abstract

When a human myeloid cell line, U937, was incubated with etoposide (10 micrograms/mL), morphologically apoptotic cells first appeared at 3 hr and increased with time to 50% at 6 hr. Pretreatment of U937 cells for 30 min with a potent tyrosine kinase inhibitor, herbimycin A (10 microM), significantly suppressed the appearance of apoptotic morphological changes. Concomitantly, herbimycin A pretreatment prevented both high molecular weight and internucleosomal DNA fragmentation induced by etoposide. Two major bands at 30 and 66 kDa with enhanced tyrosine phosphorylation inhibited by herbimycin A were detectable after 30 min of incubation with etoposide. In addition, herbimycin A prevented etoposide-induced NF-kappa B activation. The expressions of Bcl-2 and Bax, on the other hand, were not affected by herbimycin A pretreatment. Herbimycin A was also found to inhibit 1-beta-D-arabinofuranosylcytosine-induced apoptotic changes and NF-kappa B activation. These results suggest that activation of tyrosine kinase(s) may play an important role in apoptotic processes induced by a variety of anti-cancer drugs.

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Citations

Sep 29, 2000·Biochemical Pharmacology·V BoursM P Merville
Sep 29, 2000·Biochemical Pharmacology·B B Aggarwal
Nov 30, 2006·Neoplasia : an International Journal for Oncology Research·Michael B ArmstrongValerie P Castle
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May 27, 2006·Biochemical Pharmacology·Marie-Berthe MaesIngrid De Meester

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