The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine
(1) Background: Decitabine and azacitidine are cytosine analogues representing the class of drugs interfering with DNA methylation. Due to their molecular homology and similar clinical application, both drugs are often regarded as interchangeable. Despite their unique mechanism of action the studies...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/6/1530 |
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| author | Alicja Pawlak Kinga Chybicka Ewa Zioło Leon Strządała Wojciech Kałas |
| author_facet | Alicja Pawlak Kinga Chybicka Ewa Zioło Leon Strządała Wojciech Kałas |
| author_sort | Alicja Pawlak |
| collection | DOAJ |
| description | (1) Background: Decitabine and azacitidine are cytosine analogues representing the class of drugs interfering with DNA methylation. Due to their molecular homology and similar clinical application, both drugs are often regarded as interchangeable. Despite their unique mechanism of action the studies designed for observation and comparison of the prolonged activity of these drugs are rare. (2) Methods: The short-time (20–72 h) and long-term (up to 20 days) anti-cancer activity of decitabine and azacitidine has been studied in colorectal cancer cells. We observe the impact on cell culture’s viability, clonogenicity, proliferation, and expression of <i>CDKN1A, CCND1, MDM2, MYC, CDKN2A, GLB1</i> genes, and activity of SA-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula>-galactosidase. (3) Results: Decitabine has much stronger anti-clonogenic activity than azacitidine. We show that azacitidine, despite significant immediate toxicity, has negligible long-term effects. Contrary, decitabine, which does not exert initial toxicity, profoundly worsened the condition of the cells over time. On the 13th day after treatment, the viability of cells was decreased and proliferation inhibited. These functional changes were accompanied by up-regulation of expression <i>CDKN1A, CCND1, and CDKN2A</i> genes and increased activation of SA-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula>-galactosidase, indicating cellular senescence. (4) Conclusions: Our head-to-head comparison revealed profound differences in the activities of decitabine and azacitidine important in their anti-cancer potential and clinical application. The effects of decitabine need relatively long time to develop. This property is crucial for proper design of studies and therapy concerning decitabine and undermines opinion about the similar therapeutic mechanism and interchangeability of these drugs. |
| first_indexed | 2024-03-09T13:47:41Z |
| format | Article |
| id | doaj.art-f57e8be3c55a49e2bbfda62b10e6b987 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:47:41Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
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| series | Cancers |
| spelling | doaj.art-f57e8be3c55a49e2bbfda62b10e6b9872023-11-30T20:56:42ZengMDPI AGCancers2072-66942022-03-01146153010.3390/cancers14061530The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or AzacitidineAlicja Pawlak0Kinga Chybicka1Ewa Zioło2Leon Strządała3Wojciech Kałas4Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wroclaw, PolandLudwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wroclaw, PolandLudwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wroclaw, PolandLudwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wroclaw, PolandLudwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wroclaw, Poland(1) Background: Decitabine and azacitidine are cytosine analogues representing the class of drugs interfering with DNA methylation. Due to their molecular homology and similar clinical application, both drugs are often regarded as interchangeable. Despite their unique mechanism of action the studies designed for observation and comparison of the prolonged activity of these drugs are rare. (2) Methods: The short-time (20–72 h) and long-term (up to 20 days) anti-cancer activity of decitabine and azacitidine has been studied in colorectal cancer cells. We observe the impact on cell culture’s viability, clonogenicity, proliferation, and expression of <i>CDKN1A, CCND1, MDM2, MYC, CDKN2A, GLB1</i> genes, and activity of SA-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula>-galactosidase. (3) Results: Decitabine has much stronger anti-clonogenic activity than azacitidine. We show that azacitidine, despite significant immediate toxicity, has negligible long-term effects. Contrary, decitabine, which does not exert initial toxicity, profoundly worsened the condition of the cells over time. On the 13th day after treatment, the viability of cells was decreased and proliferation inhibited. These functional changes were accompanied by up-regulation of expression <i>CDKN1A, CCND1, and CDKN2A</i> genes and increased activation of SA-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula>-galactosidase, indicating cellular senescence. (4) Conclusions: Our head-to-head comparison revealed profound differences in the activities of decitabine and azacitidine important in their anti-cancer potential and clinical application. The effects of decitabine need relatively long time to develop. This property is crucial for proper design of studies and therapy concerning decitabine and undermines opinion about the similar therapeutic mechanism and interchangeability of these drugs.https://www.mdpi.com/2072-6694/14/6/1530azacitidinedecitabinecolon cancerepigenetic drugcellular senescencechemotherapy |
| spellingShingle | Alicja Pawlak Kinga Chybicka Ewa Zioło Leon Strządała Wojciech Kałas The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine Cancers azacitidine decitabine colon cancer epigenetic drug cellular senescence chemotherapy |
| title | The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine |
| title_full | The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine |
| title_fullStr | The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine |
| title_full_unstemmed | The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine |
| title_short | The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine |
| title_sort | contrasting delayed effects of transient exposure of colorectal cancer cells to decitabine or azacitidine |
| topic | azacitidine decitabine colon cancer epigenetic drug cellular senescence chemotherapy |
| url | https://www.mdpi.com/2072-6694/14/6/1530 |
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