Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis.

Abstract

Apoptosis is regarded as a suicidal cell response since the dying cell appears to be an active participant. Previous studies have shown that apoptosis of various murine cell types, induced by a variety of stimuli, required RNA and/or protein synthesis. However, when human promyelocytic leukemia HL-60 cells were induced to undergo apoptosis by treatment with the calcium ionophore A23187 or microtubule-disrupting agents, in the presence of inhibitors of macromolecular synthesis, apoptosis of these cells was neither abrogated nor delayed. Furthermore, the presence of either cycloheximide, an inhibitor of protein synthesis, or actinomycin D, an RNA synthesis inhibitor, alone was found to induce large scale apoptosis of these cells. Apoptosis in these cells was characterized by cell and chromatin condensation followed by nuclear and DNA fragmentation. In common with many other studies, this DNA fragmentation was found to have an approximately 200-bp multiple pattern, which is consistent with the activation of an endogenous endonuclease which cleaves at internucleosomal sites. Calcium-dependent endonuclease activity of this type was also detected in the isolated nuclei of untreated HL-60 cells. The morphologic and biochemical changes characteristic of apoptosis were found to precede cell death, as measured by trypan blue uptake and were completely distinct from death caused by toxic stimuli such as azide, ethanol, or heat treatment. Similar experiments with six other human cell lines confirmed that this phenomenon was not peculiar to the HL-60 cell line. These results suggest that certain dividing cell populations do not require RNA or protein synthesis to undergo apoptosis and further, that continuous transcription and translation of some regulatory protein(s) may be required to maintain control over the apoptotic "machinery" of such cells.

Regulatory networks upon neurogenesis induction in PC12 cell line by small molecules

“…Further, we have also detected the repression of POLR2A in the presence of PACAP. It is known that in response to several stress signals, cells undergo apoptosis via inhibition of RNA synthesis (Martin, Lennon, Bonham, & Cotter, ). Therefore, in agreement with our results, inhibiting POLRD2A expression was known as a hallmark for the commencing of apoptosis in neurons.…”

Current Concepts in Cell Death

“…This may suggest a possible role for HSPs in the resistance mechanism. Furthermore, HSPs are also implicated in drug resistance (McClean and Hill, 1992) and heatshocked or HSP-overexpressing cells become more resistant to the cytotoxic effects of some anticancer drugs (Oesterreich et al, 1993) that are otherwise capable of inducing both apoptosis and necrosis (Martin et al, 1990).…”

Current Concepts in Cell Toxicity

“…This may suggest a possible role for HSPs in the resistance mechanism. Furthermore, HSPs are also implicated in drug resistance (McClean and Hill, 1992), and heat-shocked or HSP-overexpressing cells become more resistant to the cytotoxic effects of some anticancer drugs (Oesterreich et al, 1993) that are otherwise capable of inducing both apoptosis and necrosis (Martin et al, 1990).…”