Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy
The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cy...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/4159013 |
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| author | Marco Malavolta Massimo Bracci Lory Santarelli Md Abu Sayeed Elisa Pierpaoli Robertina Giacconi Laura Costarelli Francesco Piacenza Andrea Basso Maurizio Cardelli Mauro Provinciali |
| author_facet | Marco Malavolta Massimo Bracci Lory Santarelli Md Abu Sayeed Elisa Pierpaoli Robertina Giacconi Laura Costarelli Francesco Piacenza Andrea Basso Maurizio Cardelli Mauro Provinciali |
| author_sort | Marco Malavolta |
| collection | DOAJ |
| description | The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms) that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity. |
| format | Article |
| id | doaj-art-b66c35a74a604cb3acbbf42c0d63bb85 |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b66c35a74a604cb3acbbf42c0d63bb852025-08-20T03:20:54ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/41590134159013Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant TherapyMarco Malavolta0Massimo Bracci1Lory Santarelli2Md Abu Sayeed3Elisa Pierpaoli4Robertina Giacconi5Laura Costarelli6Francesco Piacenza7Andrea Basso8Maurizio Cardelli9Mauro Provinciali10Advanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyDepartment of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, ItalyDepartment of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, ItalyDepartment of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, ItalyAdvanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyAdvanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyAdvanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyAdvanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyAdvanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyAdvanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyAdvanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, ItalyThe reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms) that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity.http://dx.doi.org/10.1155/2018/4159013 |
| spellingShingle | Marco Malavolta Massimo Bracci Lory Santarelli Md Abu Sayeed Elisa Pierpaoli Robertina Giacconi Laura Costarelli Francesco Piacenza Andrea Basso Maurizio Cardelli Mauro Provinciali Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy Mediators of Inflammation |
| title | Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy |
| title_full | Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy |
| title_fullStr | Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy |
| title_full_unstemmed | Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy |
| title_short | Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy |
| title_sort | inducers of senescence toxic compounds and senolytics the multiple faces of nrf2 activating phytochemicals in cancer adjuvant therapy |
| url | http://dx.doi.org/10.1155/2018/4159013 |
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