Multiple pathways are involved in protection of MCF‐7 cells against death due to protein synthesis inhibition

Avraham Geier*, Chana Weiss, Rachel Beery, Michal Haimsohn, Rina Hemi, Zvi Malik, Avraham Karasik

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Previously we have shown that IGF‐1 protected MCF‐7 cells against death induced by the protein synthesis inhibitor cycloheximide (CHX). In the present study we investigated the ability of protein kinase C activator 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA), the protein kinase A activator 8‐bromoadenosine 3′5′‐cyclic monophosphate (Br‐cAMP), and the enzyme inhibitor aurintricarboxylic acid (ATA) to protect MCF‐7 cells against death, due to a continuous presence of CHX. Cell death was evaluated after 48 h of incubation by several techniques (trypan blue staining, release of lactic dehydrogenase, cellular ATP content, transmission electron microscopy, and DNA fragmentation). Apoptosis which terminates in necrosis, characterized this mode of cell death. TPA and ATA at optimal concentrations of 40 ng/ml and 100 μg/ml, respectively, reduced cell death to the control level (without CHX), while Br‐cAMP at an optimal concentration of 650 μg/ml reduced cell death only partially. IGF‐1, TPA, and ATA, which stimulated protein synthesis in the control MCF‐7 cells, had no effect on protein synthesis in the CHX‐treated cells, indicating that the survival effect is not due to new protein synthesis. The protein kinase C inhibitor staurosporine blocked the survival effect of TPA and IGF‐1 in a dose‐dependent manner, however did not affect the survival effect of ATA. The tyrosine kinase inhibitor genistein blocked the survival effect of IGF‐1, but not that of TPA and ATA. Our results provide evidence for several distinctive pathways, the activation of which protects MCF‐7 cells against death, due to protein synthesis inhibition. © 1995 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)570-576
Number of pages7
JournalJournal of Cellular Physiology
Issue number3
StatePublished - Jun 1995
Externally publishedYes


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