Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics
In this paper we review the mechanisms of the antitumor effects of <i>Hypericum perforatum</i> L. (St. John’s wort, SJW) and its main active component hyperforin (HPF). SJW extract is commonly employed as antidepressant due to its ability to inhibit monoamine neurotransmitters re-uptake....
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/1/18 |
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| author | Marta Menegazzi Pellegrino Masiello Michela Novelli |
| author_facet | Marta Menegazzi Pellegrino Masiello Michela Novelli |
| author_sort | Marta Menegazzi |
| collection | DOAJ |
| description | In this paper we review the mechanisms of the antitumor effects of <i>Hypericum perforatum</i> L. (St. John’s wort, SJW) and its main active component hyperforin (HPF). SJW extract is commonly employed as antidepressant due to its ability to inhibit monoamine neurotransmitters re-uptake. Moreover, further biological properties make this vegetal extract very suitable for both prevention and treatment of several diseases, including cancer. Regular use of SJW reduces colorectal cancer risk in humans and prevents genotoxic effects of carcinogens in animal models. In established cancer, SJW and HPF can still exert therapeutic effects by their ability to downregulate inflammatory mediators and inhibit pro-survival kinases, angiogenic factors and extracellular matrix proteases, thereby counteracting tumor growth and spread. Remarkably, the mechanisms of action of SJW and HPF include their ability to decrease ROS production and restore pH imbalance in tumor cells. The SJW component HPF, due to its high lipophilicity and mild acidity, accumulates in membranes and acts as a protonophore that hinders inner mitochondrial membrane hyperpolarization, inhibiting mitochondrial ROS generation and consequently tumor cell proliferation. At the plasma membrane level, HPF prevents cytosol alkalization and extracellular acidification by allowing protons to re-enter the cells. These effects can revert or at least attenuate cancer cell phenotype, contributing to hamper proliferation, neo-angiogenesis and metastatic dissemination. Furthermore, several studies report that in tumor cells SJW and HPF, mainly at high concentrations, induce the mitochondrial apoptosis pathway, likely by collapsing the mitochondrial membrane potential. Based on these mechanisms, we highlight the SJW/HPF remarkable potentiality in cancer prevention and treatment. |
| first_indexed | 2024-03-10T13:44:44Z |
| format | Article |
| id | doaj.art-a15957486a8942938fdcda916447d4f6 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T13:44:44Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-a15957486a8942938fdcda916447d4f62023-11-21T02:45:35ZengMDPI AGAntioxidants2076-39212020-12-011011810.3390/antiox10010018Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton DynamicsMarta Menegazzi0Pellegrino Masiello1Michela Novelli2Department of Neuroscience, Biomedicine and Movement Sciences, Biochemistry Section, School of Medicine, University of Verona, Strada Le Grazie 8, I-37134 Verona, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Via Roma 55, I-56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Via Roma 55, I-56126 Pisa, ItalyIn this paper we review the mechanisms of the antitumor effects of <i>Hypericum perforatum</i> L. (St. John’s wort, SJW) and its main active component hyperforin (HPF). SJW extract is commonly employed as antidepressant due to its ability to inhibit monoamine neurotransmitters re-uptake. Moreover, further biological properties make this vegetal extract very suitable for both prevention and treatment of several diseases, including cancer. Regular use of SJW reduces colorectal cancer risk in humans and prevents genotoxic effects of carcinogens in animal models. In established cancer, SJW and HPF can still exert therapeutic effects by their ability to downregulate inflammatory mediators and inhibit pro-survival kinases, angiogenic factors and extracellular matrix proteases, thereby counteracting tumor growth and spread. Remarkably, the mechanisms of action of SJW and HPF include their ability to decrease ROS production and restore pH imbalance in tumor cells. The SJW component HPF, due to its high lipophilicity and mild acidity, accumulates in membranes and acts as a protonophore that hinders inner mitochondrial membrane hyperpolarization, inhibiting mitochondrial ROS generation and consequently tumor cell proliferation. At the plasma membrane level, HPF prevents cytosol alkalization and extracellular acidification by allowing protons to re-enter the cells. These effects can revert or at least attenuate cancer cell phenotype, contributing to hamper proliferation, neo-angiogenesis and metastatic dissemination. Furthermore, several studies report that in tumor cells SJW and HPF, mainly at high concentrations, induce the mitochondrial apoptosis pathway, likely by collapsing the mitochondrial membrane potential. Based on these mechanisms, we highlight the SJW/HPF remarkable potentiality in cancer prevention and treatment.https://www.mdpi.com/2076-3921/10/1/18<i>Hypericum perforatum</i>hyperforinreactive oxygen speciespH regulationtumor preventiontumor therapy |
| spellingShingle | Marta Menegazzi Pellegrino Masiello Michela Novelli Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics Antioxidants <i>Hypericum perforatum</i> hyperforin reactive oxygen species pH regulation tumor prevention tumor therapy |
| title | Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics |
| title_full | Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics |
| title_fullStr | Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics |
| title_full_unstemmed | Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics |
| title_short | Anti-Tumor Activity of <i>Hypericum perforatum</i> L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics |
| title_sort | anti tumor activity of i hypericum perforatum i l and hyperforin through modulation of inflammatory signaling ros generation and proton dynamics |
| topic | <i>Hypericum perforatum</i> hyperforin reactive oxygen species pH regulation tumor prevention tumor therapy |
| url | https://www.mdpi.com/2076-3921/10/1/18 |
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