Hyperforin Induces Apoptosis Through Extrinsic/Intrinsic Pathways and Inhibits NF-ĸB-modulated Survival and Invasion Potential in Bladder Cancer

Abstract

Background/Aim: Muscle-invasive bladder cancer (MIBC) has long been recognized as a difficult to treat cancer type, thus a new treatment strategy is needed. The major purpose of the present study was to verify the anticancer effect of hyperforin and the mechanism through which it affects tumor cell growth and invasion in bladder cancer in vitro. Materials and Methods: Bladder cancer TSGH-8301 cells were treated with different concentrations of hyperforin for different durations of time. The changes in cell viability, production of calcium and reactive oxygen species (ROS), and anti-apoptotic signaling were evaluated using MTT assay, flow cytometry, and western blot analysis. The effect of hyperforin on the expression of nuclear factor-kappaB (NF-ĸB) p65 (Ser276), tumor progression-associated proteins, as well as on cell invasion was investigated using western blotting and cell invasion assay, respectively. Results: Hyperforin significantly induces apoptosis, extrinsic/intrinsic apoptotic signaling,

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

“…Actually, it has been documented that SJW extract promotes apoptosis and decreases NF-κB protein level in MCF-7 cells [ 170 ] and that SJW oil inhibits NF-κB activation in human chronic myelogenous leukemia K562 cells [ 171 ]. HPF decreases the expression level of anti-apoptotic proteins and induces apoptotic cell death through blockade of NF-κB activity in non-small cell lung cancer [ 147 ], bladder cancer [ 172 ] and U-87 and GBM-8401 glioblastoma [ 161 ] cell lines. In order to clarify the molecular mechanism leading to NF-κB inhibition by HPF, it should be reminded that this transcription factor can be activated by inflammatory mediators through ROS as second messengers [ 57 , 59 ].…”

Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma

“…Kim et al and others point to the critical role of ROS production (via NOX1 and NOX4) and subsequent NF-κB induction in invasive processes of bladder cancer cells in vitro and in vivo [ 82 , 83 ]. In contrast, suppression of NF-αB has provoked apoptosis and diminished metastatic properties of bladder cancer in vitro [ 84 ]. In a preclinical investigation NF-κB was associated with a poor prognosis, leading to the consideration that NF-κB may serve as a prognostic biomarker in bladder cancer patients [ 85 ].…”

Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials

“…Additionally, hypericum extracts have been reported to have a protective effect on the brain, improve anxiety-like behavior (Sevastre-Berghian et al 2018 ) and exhibit an antidepressant-like activity in mice (Pochwat et al 2018 ). Besides, as a specific activator for TRPC6, hyperforin usage could reduce the growth and viability of the various human and rat cancer cell lines by apoptosis with IC 50 between 3 and 15 μM (Schempp et al 2002 ; Chen et al 2018 ; Liu et al 2019 ). The anti-tumor activity of H. perforatum L. and hyperforin has been proven to be linked with mediating inflammatory signaling, ROS generation, and proton dynamics, as well as exhibiting antiproliferative effects (Allegra and Tonacci 2020 ).…”

“…The anti-tumor activity of H. perforatum L. and hyperforin has been proven to be linked with mediating inflammatory signaling, ROS generation, and proton dynamics, as well as exhibiting antiproliferative effects (Allegra and Tonacci 2020 ). Hyperforin causes apoptosis through extrinsic/intrinsic pathways and inhibits NF-κB-mediated invasion, enhancing the survival potential in bladder cancer and non-small cell lung cancer (Chen et al 2018 ; Liu et al 2019 ); it also inhibits the EGFR/ERK/NF-κB-modulated anti-apoptotic potential in glioblastoma (Hsu et al 2020 ). Hyperforin could prevent parental and oxaliplatin-resistant human adenocarcinoma cells’ metastasis through anti-adhesion therapy (Šemeláková et al 2018 ).…”