Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence
Aspirin and its main metabolite salicylate are promising molecules in preventing cancer and metabolic diseases. S. cerevisiae cells have been used to study some of their effects: (i) salicylate induces the reversible inhibition of both glucose transport and the biosyntheses of glucose-derived sugar...
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2018-03-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/antagonism-between-salicylate-and-the-camp-signal-controls-yeast-cell-survival-and-growth-recovery-from-quiescence/ |
| _version_ | 1826532114681561088 |
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| author | Maurizio D. Baroni Sonia Colombo Enzo Martegani |
| author_facet | Maurizio D. Baroni Sonia Colombo Enzo Martegani |
| author_sort | Maurizio D. Baroni |
| collection | DOAJ |
| description | Aspirin and its main metabolite salicylate are promising molecules in preventing cancer and metabolic diseases. S. cerevisiae cells have been used to study some of their effects: (i) salicylate induces the reversible inhibition of both glucose transport and the biosyntheses of glucose-derived sugar phosphates, (ii) Aspirin/salicylate causes apoptosis associated with superoxide radical accumulation or early cell necrosis in MnSOD-deficient cells growing in ethanol or in glucose, respectively. So, treatment with (acetyl)-salicylic acid can alter the yeast metabolism and is associated with cell death. We describe here the dramatic effects of salicylate on cellular control of the exit from a quiescence state. The growth recovery of long-term stationary phase cells was strongly inhibited in the presence of salicylate, to a degree proportional to the drug concentration. At high salicylate concentration, growth reactivation was completely repressed and associated with a dramatic loss of cell viability. Strikingly, both of these phenotypes were fully suppressed by increasing the cAMP signal without any variation of the exponential growth rate. Upon nutrient exhaustion, salicylate induced a premature lethal cell cycle arrest in the budded-G2/M phase that cannot be suppressed by PKA activation. We discuss how the dramatic antagonism between cAMP and salicylate could be conserved and impinge common targets in yeast and humans. Targeting quiescence of cancer cells with stem-like properties and their growth recovery from dormancy are major challenges in cancer therapy. If mechanisms underlying cAMP-salicylate antagonism will be defined in our model, this might have significant therapeutic implications. |
| first_indexed | 2024-12-23T04:55:52Z |
| format | Article |
| id | doaj.art-964845bc277f4b9eb3166e7aec59f96c |
| institution | Directory Open Access Journal |
| issn | 2311-2638 |
| language | English |
| last_indexed | 2025-03-14T01:46:05Z |
| publishDate | 2018-03-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj.art-964845bc277f4b9eb3166e7aec59f96c2025-03-12T13:46:40ZengShared Science Publishers OGMicrobial Cell2311-26382018-03-015734435610.15698/mic2018.07.640Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescenceMaurizio D. Baroni0Sonia Colombo1Enzo Martegani2Dipartimento di Biologia, Università di Padova, 35133 Padova, Italy.Dipartimento di Biotecnologie e Bioscienze, Università Milano Bicocca, 20126 Milano, Italy.Dipartimento di Biotecnologie e Bioscienze, Università Milano Bicocca, 20126 Milano, Italy.Aspirin and its main metabolite salicylate are promising molecules in preventing cancer and metabolic diseases. S. cerevisiae cells have been used to study some of their effects: (i) salicylate induces the reversible inhibition of both glucose transport and the biosyntheses of glucose-derived sugar phosphates, (ii) Aspirin/salicylate causes apoptosis associated with superoxide radical accumulation or early cell necrosis in MnSOD-deficient cells growing in ethanol or in glucose, respectively. So, treatment with (acetyl)-salicylic acid can alter the yeast metabolism and is associated with cell death. We describe here the dramatic effects of salicylate on cellular control of the exit from a quiescence state. The growth recovery of long-term stationary phase cells was strongly inhibited in the presence of salicylate, to a degree proportional to the drug concentration. At high salicylate concentration, growth reactivation was completely repressed and associated with a dramatic loss of cell viability. Strikingly, both of these phenotypes were fully suppressed by increasing the cAMP signal without any variation of the exponential growth rate. Upon nutrient exhaustion, salicylate induced a premature lethal cell cycle arrest in the budded-G2/M phase that cannot be suppressed by PKA activation. We discuss how the dramatic antagonism between cAMP and salicylate could be conserved and impinge common targets in yeast and humans. Targeting quiescence of cancer cells with stem-like properties and their growth recovery from dormancy are major challenges in cancer therapy. If mechanisms underlying cAMP-salicylate antagonism will be defined in our model, this might have significant therapeutic implications.http://microbialcell.com/researcharticles/antagonism-between-salicylate-and-the-camp-signal-controls-yeast-cell-survival-and-growth-recovery-from-quiescence/Salicylatecyclic AMPcellular growthcell deathyeastNSAIDs |
| spellingShingle | Maurizio D. Baroni Sonia Colombo Enzo Martegani Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence Microbial Cell Salicylate cyclic AMP cellular growth cell death yeast NSAIDs |
| title | Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence |
| title_full | Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence |
| title_fullStr | Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence |
| title_full_unstemmed | Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence |
| title_short | Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence |
| title_sort | antagonism between salicylate and the camp signal controls yeast cell survival and growth recovery from quiescence |
| topic | Salicylate cyclic AMP cellular growth cell death yeast NSAIDs |
| url | http://microbialcell.com/researcharticles/antagonism-between-salicylate-and-the-camp-signal-controls-yeast-cell-survival-and-growth-recovery-from-quiescence/ |
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