Anti-Tumor Activity of Hypericum perforatum L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics

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.

Hyperforin and Myrtucommulone Derivatives Act as Natural Modulators of Wnt/β-Catenin Signaling in HCT116 Colon Cancer Cells

“…In recent years, the anti-inflammatory and anti-cancer activities of HF and myrtucommulones have also come into focus (for review, see [ 7 , 9 , 10 ]). In this respect, HF has been shown to act as a potent cyclooxygenase-1 and 5-lipoxygenase inhibitor [ 11 , 12 ].…”

Application Potential of Plant-Derived Medicines in Prevention and Treatment of Platinum-Induced Peripheral Neurotoxicity

“…Hypericum perforatum L. (Saint John’s Wort) is one of the most widely prescribed agents in natural remedies and has been used for centuries worldwide ( Menegazzi et al, 2020 ). Notably, although it is a famous medicinal plant, this plant is not absolutely safe.…”

How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology?

“…The pharmacological properties of Hypericum perforatum are associated mainly with hyperforin (HPF) and hypericin, which usually present in a total hydro-alcoholic HP extract concentrations ranging between 1 and 5% and 0.1 and 0.3%, respectively [ 274 ]. Other HP constituents are hyperoside, rutin, quercetin, catechin polyphenols, acylphloroglucinols, and naphthodianthrones [ 275 ].…”

“…It also reduces ROS [ 278 ] and genotoxic stress [ 279 ]. These, and other, properties of HP protect from carcinogenesis [ 274 ].…”