Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis
The role of mitochondria as the electric engine of cells is well established. Over the past two decades, accumulating evidence has pointed out that, despite the presence of a highly active glycolytic pathway (Warburg effect), a functional and even upregulated mitochondrial respiration occurs in canc...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/14/1/115 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832589236547616768 |
|---|---|
| author | Raffaella Chiaramonte Giulia Sauro Domenica Giannandrea Patrizia Limonta Lavinia Casati |
| author_facet | Raffaella Chiaramonte Giulia Sauro Domenica Giannandrea Patrizia Limonta Lavinia Casati |
| author_sort | Raffaella Chiaramonte |
| collection | DOAJ |
| description | The role of mitochondria as the electric engine of cells is well established. Over the past two decades, accumulating evidence has pointed out that, despite the presence of a highly active glycolytic pathway (Warburg effect), a functional and even upregulated mitochondrial respiration occurs in cancer cells to meet the need of high energy and the biosynthetic demand to sustain their anabolic growth. Mitochondria are also the primary source of intracellular ROS. Cancer cells maintain moderate levels of ROS to promote tumorigenesis, metastasis, and drug resistance; indeed, once the cytotoxicity threshold is exceeded, ROS trigger oxidative damage, ultimately leading to cell death. Based on this, mitochondrial metabolic functions and ROS generation are considered attractive targets of synthetic and natural anticancer compounds. Tocotrienols (TTs), specifically the δ- and γ-TT isoforms, are vitamin E-derived biomolecules widely shown to possess striking anticancer properties since they regulate several intracellular molecular pathways. Herein, we provide for the first time an overview of the mitochondrial metabolic reprogramming and redox homeostasis perturbation occurring in cancer cells, highlighting their involvement in the anticancer properties of TTs. This evidence sheds light on the use of these natural compounds as a promising preventive or therapeutic approach for novel anticancer strategies. |
| format | Article |
| id | doaj-art-15cfb399ebe94f6fa10ec532feeedb23 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-15cfb399ebe94f6fa10ec532feeedb232025-01-24T13:19:32ZengMDPI AGAntioxidants2076-39212025-01-0114111510.3390/antiox14010115Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox HomeostasisRaffaella Chiaramonte0Giulia Sauro1Domenica Giannandrea2Patrizia Limonta3Lavinia Casati4Department of Health Sciences, Università degli Studi di Milano, 20142 Milan, ItalyDepartment of Health Sciences, Università degli Studi di Milano, 20142 Milan, ItalyDepartment of Health Sciences, Università degli Studi di Milano, 20142 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences “R. Paoletti”, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Health Sciences, Università degli Studi di Milano, 20142 Milan, ItalyThe role of mitochondria as the electric engine of cells is well established. Over the past two decades, accumulating evidence has pointed out that, despite the presence of a highly active glycolytic pathway (Warburg effect), a functional and even upregulated mitochondrial respiration occurs in cancer cells to meet the need of high energy and the biosynthetic demand to sustain their anabolic growth. Mitochondria are also the primary source of intracellular ROS. Cancer cells maintain moderate levels of ROS to promote tumorigenesis, metastasis, and drug resistance; indeed, once the cytotoxicity threshold is exceeded, ROS trigger oxidative damage, ultimately leading to cell death. Based on this, mitochondrial metabolic functions and ROS generation are considered attractive targets of synthetic and natural anticancer compounds. Tocotrienols (TTs), specifically the δ- and γ-TT isoforms, are vitamin E-derived biomolecules widely shown to possess striking anticancer properties since they regulate several intracellular molecular pathways. Herein, we provide for the first time an overview of the mitochondrial metabolic reprogramming and redox homeostasis perturbation occurring in cancer cells, highlighting their involvement in the anticancer properties of TTs. This evidence sheds light on the use of these natural compounds as a promising preventive or therapeutic approach for novel anticancer strategies.https://www.mdpi.com/2076-3921/14/1/115cancer cellsmitochondrial metabolic reprogrammingROS generationredox homeostasistocotrienolsanticancer activity |
| spellingShingle | Raffaella Chiaramonte Giulia Sauro Domenica Giannandrea Patrizia Limonta Lavinia Casati Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis Antioxidants cancer cells mitochondrial metabolic reprogramming ROS generation redox homeostasis tocotrienols anticancer activity |
| title | Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis |
| title_full | Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis |
| title_fullStr | Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis |
| title_full_unstemmed | Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis |
| title_short | Molecular Insights in the Anticancer Activity of Natural Tocotrienols: Targeting Mitochondrial Metabolism and Cellular Redox Homeostasis |
| title_sort | molecular insights in the anticancer activity of natural tocotrienols targeting mitochondrial metabolism and cellular redox homeostasis |
| topic | cancer cells mitochondrial metabolic reprogramming ROS generation redox homeostasis tocotrienols anticancer activity |
| url | https://www.mdpi.com/2076-3921/14/1/115 |
| work_keys_str_mv | AT raffaellachiaramonte molecularinsightsintheanticanceractivityofnaturaltocotrienolstargetingmitochondrialmetabolismandcellularredoxhomeostasis AT giuliasauro molecularinsightsintheanticanceractivityofnaturaltocotrienolstargetingmitochondrialmetabolismandcellularredoxhomeostasis AT domenicagiannandrea molecularinsightsintheanticanceractivityofnaturaltocotrienolstargetingmitochondrialmetabolismandcellularredoxhomeostasis AT patrizialimonta molecularinsightsintheanticanceractivityofnaturaltocotrienolstargetingmitochondrialmetabolismandcellularredoxhomeostasis AT laviniacasati molecularinsightsintheanticanceractivityofnaturaltocotrienolstargetingmitochondrialmetabolismandcellularredoxhomeostasis |