Impact of local anesthetics on epigenetics in cancer
Defective silencing of tumor suppressor genes through epigenetic alterations contributes to oncogenesis by perturbing cell cycle regulation, DNA repair or cell death mechanisms. Reversal of such epigenetic changes including DNA hypermethylation provides a promising anticancer strategy. Until now, th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.849895/full |
| _version_ | 1818494789725716480 |
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| author | Lucillia Bezu Lucillia Bezu Lucillia Bezu Oliver Kepp Oliver Kepp Guido Kroemer Guido Kroemer Guido Kroemer |
| author_facet | Lucillia Bezu Lucillia Bezu Lucillia Bezu Oliver Kepp Oliver Kepp Guido Kroemer Guido Kroemer Guido Kroemer |
| author_sort | Lucillia Bezu |
| collection | DOAJ |
| description | Defective silencing of tumor suppressor genes through epigenetic alterations contributes to oncogenesis by perturbing cell cycle regulation, DNA repair or cell death mechanisms. Reversal of such epigenetic changes including DNA hypermethylation provides a promising anticancer strategy. Until now, the nucleoside derivatives 5-azacytidine and decitabine are the sole DNA methyltransferase (DNMT) inhibitors approved by the FDA for the treatment of specific hematological cancers. Nevertheless, due to their nucleoside structure, these inhibitors directly incorporate into DNA, which leads to severe side effects and compromises genomic stability. Much emphasis has been placed on the development of less toxic epigenetic modifiers. Recently, several preclinical studies demonstrated the potent epigenetic effects of local anesthetics, which are routinely used during primary tumor resection to relief surgical pain. These non-nucleoside molecules inhibit DNMT activity, affect the expression of micro-RNAs and repress histone acetylation, thus exerting cytotoxic effects on malignant cells. The in-depth mechanistic comprehension of these epigenetic effects might promote the use of local anesthetics as anticancer drugs. |
| first_indexed | 2024-12-10T18:11:14Z |
| format | Article |
| id | doaj.art-df2e5830c315402cb19109efb8801246 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T18:11:14Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-df2e5830c315402cb19109efb88012462022-12-22T01:38:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.849895849895Impact of local anesthetics on epigenetics in cancerLucillia Bezu0Lucillia Bezu1Lucillia Bezu2Oliver Kepp3Oliver Kepp4Guido Kroemer5Guido Kroemer6Guido Kroemer7Equipe Labellisée Par La Ligue Contre Le Cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, FranceMetabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, FranceService d’Anesthésie Gustave Roussy Cancer Campus, Villejuif, FranceEquipe Labellisée Par La Ligue Contre Le Cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, FranceMetabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, FranceEquipe Labellisée Par La Ligue Contre Le Cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, FranceMetabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, FrancePôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, FranceDefective silencing of tumor suppressor genes through epigenetic alterations contributes to oncogenesis by perturbing cell cycle regulation, DNA repair or cell death mechanisms. Reversal of such epigenetic changes including DNA hypermethylation provides a promising anticancer strategy. Until now, the nucleoside derivatives 5-azacytidine and decitabine are the sole DNA methyltransferase (DNMT) inhibitors approved by the FDA for the treatment of specific hematological cancers. Nevertheless, due to their nucleoside structure, these inhibitors directly incorporate into DNA, which leads to severe side effects and compromises genomic stability. Much emphasis has been placed on the development of less toxic epigenetic modifiers. Recently, several preclinical studies demonstrated the potent epigenetic effects of local anesthetics, which are routinely used during primary tumor resection to relief surgical pain. These non-nucleoside molecules inhibit DNMT activity, affect the expression of micro-RNAs and repress histone acetylation, thus exerting cytotoxic effects on malignant cells. The in-depth mechanistic comprehension of these epigenetic effects might promote the use of local anesthetics as anticancer drugs.https://www.frontiersin.org/articles/10.3389/fonc.2022.849895/fulllocal anestheticsepigeneticcancerdemethylationmiRNA |
| spellingShingle | Lucillia Bezu Lucillia Bezu Lucillia Bezu Oliver Kepp Oliver Kepp Guido Kroemer Guido Kroemer Guido Kroemer Impact of local anesthetics on epigenetics in cancer Frontiers in Oncology local anesthetics epigenetic cancer demethylation miRNA |
| title | Impact of local anesthetics on epigenetics in cancer |
| title_full | Impact of local anesthetics on epigenetics in cancer |
| title_fullStr | Impact of local anesthetics on epigenetics in cancer |
| title_full_unstemmed | Impact of local anesthetics on epigenetics in cancer |
| title_short | Impact of local anesthetics on epigenetics in cancer |
| title_sort | impact of local anesthetics on epigenetics in cancer |
| topic | local anesthetics epigenetic cancer demethylation miRNA |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.849895/full |
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