Cycloheximide protection against actinomycin D cytotoxicity

Borrelli, Michael J.; Stafford, Diane M.; Rausch, Cynthia M.; Ofenstein, John P.; Cosenza, Stephen C.; Soprano, Kenneth J.

doi:10.1002/jcp.1041530310

Cited by 5 publications

(1 citation statement)

References 30 publications

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“…Aclacinomycin also was noted to trigger a rapid but transient decrease in the levels of c-myc and c-myb transcripts (62). c-myc downregulation has also been reported for dactinomycin (12) and for cytarabine. For cytarabine, the first peak of c-myc downregulation in K562 human erythroleukemia cells was correlated with the onset of cell differentiation (8).…”

Section: Discussionmentioning

confidence: 70%

Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation

Shishido

Wolschendorf

Duverger

et al. 2012

J Virol

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Reactivation of latent HIV-1 infection is considered our best therapeutic means to eliminate the latent HIV-1 reservoir. Past therapeutic attempts to systemically trigger HIV-1 reactivation using single drugs were unsuccessful. We thus sought to identify drug combinations consisting of one component that would lower the HIV-1 reactivation threshold and a synergistic activator. With aclacinomycin and dactinomycin, we initially identified two FDA-approved drugs that primed latent HIV-1 infection in T cell lines and in primary T cells for reactivation and facilitated complete reactivation at the population level. This effect was correlated not with the reported primary drug effects but with the cell-differentiating capacity of the drugs. We thus tested other cell-differentiating drugs/compounds such as cytarabine and aphidicolin and found that they also primed latent HIV-1 infection for reactivation. This finding extends the therapeutic promise of N ′- N ′-hexamethylene-bisacetamide (HMBA), another cell-differentiating agent that has been reported to trigger HIV-1 reactivation, into the group of FDA-approved drugs. To this end, it is also noteworthy that suberoylanilide hydroxamic acid (SAHA), a polar compound that was initially developed as a second-generation cell-differentiating agent using HMBA as a structural template and which is now marketed as the histone deacetylase (HDAC) inhibitor vorinostat, also has been reported to trigger HIV-1 reactivation. Our findings suggest that drugs with primary or secondary cell-differentiating capacity should be revisited as HIV-1-reactivating agents as some could potentially be repositioned as candidate drugs to be included in an induction therapy to trigger HIV-1 reactivation.

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Section: Discussionmentioning

confidence: 70%

Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation

Shishido

Wolschendorf

Duverger

et al. 2012

J Virol

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Characterization of a signal generated by oxidation of protein thiols that activates the heat shock transcription factor

Freeman

Borrelli

Syed

et al. 1995

Journal Cellular Physiology

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The diazenecarbonyl derivative, diamide, was used to produce nonnative protein disulfides in Chinese hamster ovary cells in order to characterize the events that occur during thiol oxidation-induced denaturation that trigger induction of Hsp 70. We limit the term protein denaturation to a process involving a conformational rearrangement by which the ordered native structure of a protein changes to a more disordered structure. Protein thiol oxidation resulted in immediate destabilization of proteins, as assessed by differential scanning calorimetry (DSC). The DSC profile indicated both a decrease in the onset temperature for detection of denaturation and destabilization of a class of proteins with an average transition temperature (Tm) of 60 degrees C. Concomitant with destabilization was an increase in proteins associated with isolated nuclei. Thiol oxidation also induced heat shock transcription factor (HSF) binding activity, however, this was nearly undetectable immediately following diamide treatment: maximum activation occurred 3 hr following exposure. In contrast, heat shock denatured thermolabile proteins which exhibited a Tm of < or = 48 degrees C. Heat shock also resulted in a rapid increase in proteins associated with isolated nuclei and produced immediate and maximum activation of HSF binding. The accumulation of Hsp and Hsc 70 mRNA following thiol oxidation reflected the delay in HSF binding. Acquisition of HSF binding activity occurred immediately if diamide-treated cells were subsequently exposed to a heat shock, indicating that HSF was not inactivated by the diamide treatment. Ostensibly, the cellular system for detecting denatured/abnormal proteins failed to immediately recognize the signal generated by thiol oxidation. These results suggest that at least two processes are involved in the induction of Hsp 70 by nonnative disulfide bond formation: destabilization of protein structure resulting in denaturation and recognition of denatured protein.

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Differential effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on αB-crystallin and hsp70 gene expression in murine cell lines

Berns

Galoforo

Erdö́s

et al. 1995

Biochemical Pharmacology

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Cycloheximide protection against actinomycin D cytotoxicity

Cited by 5 publications

References 30 publications

Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation

Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation

Characterization of a signal generated by oxidation of protein thiols that activates the heat shock transcription factor

Differential effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on αB-crystallin and hsp70 gene expression in murine cell lines

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