Abstract
In this paper we review the mechanisms of the antitumor effects of Hypericum perforatum 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.
Highlights
Despite the enormous and enduring effort undertaken by biomedical scientists in the investigation of tumor pathogenesis and therapy, cancer remains the second leading cause of death worldwide (World Health Organization, 2019 https://www.who.int/healthtopics/cancer#tab=tab_1)
Among various natural compounds endowed with antitumor properties, we want to aim attention at Hypericum perforatum L., known as St
In the same cells supplemented with St. John’s Wort (SJW) or HPF, we showed a significant concentration-dependent reduction of the phosphorylation level of several cytokineselicited kinases, such as IKK, Akt, p38, c-Jun N-terminal kinase (JNK), ERK1/2 [109]
Summary
Despite the enormous and enduring effort undertaken by biomedical scientists in the investigation of tumor pathogenesis and therapy, cancer remains the second leading cause of death worldwide (World Health Organization, 2019 https://www.who.int/healthtopics/cancer#tab=tab_1). Natural antitumor agents show a broad spectrum of mechanisms to inhibit cancer development, through reduction of proliferation rate of malignant cells, induction of apoptosis, blockade of invasiveness and neo-angiogenesis [2]. They generally display lower side effects than other antitumor drugs [3]. Among various natural compounds endowed with antitumor properties, we want to aim attention at Hypericum perforatum L., known as St. John’s wort, and its Antioxidants 2021, 10, 18. Antioxidants 2021, 10, 18 principal constituent hyperforin, by reviewing research advancements about their key molecular mechanisms and highlighting their remarkable potential in cancer prevention and treatment
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