Rapha Myr®, a Blend of Sulforaphane and Myrosinase, Exerts Antitumor and Anoikis-Sensitizing Effects on Human Astrocytoma Cells Modulating Sirtuins and DNA Methylation

Abstract

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr®) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.

The Antioxidant Activities of Betula etnensis Rafin. Ethanolic Extract Exert Protective and Anti-diabetic Effects on Streptozotocin-Induced Diabetes in Rats

“…These last results suggested an involvement of Sirt1 activation in improving insulin sensitivity following the oral administration of the extract. Our data agrees with previous in vitro and in vivo studies that demonstrated the efficacy of different plant extracts containing polyphenolic and terpenic compounds on the glycemic profile, SIRT1 activity modulation and oxidant/antioxidant status [49][50][51].…”

Protocatechuic Acid, a Simple Plant Secondary Metabolite, Induced Apoptosis by Promoting Oxidative Stress through HO-1 Downregulation and p21 Upregulation in Colon Cancer Cells

“…In addition, it has been reported that these compounds possess several other biological activities, including antimutagenic and/or anticarcinogenic properties [13]. Despite their antioxidant activity, phenolics show pro-oxidative potential because they can be converted into more reactive radicals or indirectly induce ROS overproduction through interaction with different molecular pathways [14]. In addition, this pro-oxidant activity allows us to sensitize cancer cells to oxidative stress by blocking their antioxidant defense, resulting in cell death through inhibition of Nrf2 pathways and, in turn, of its downstream effectors, such as antioxidant enzymes (SOD, catalase) and glutathione (GSH), thioredoxin, and HO-1 systems [15].…”

Wild Artichoke (Cynara cardunculus subsp. sylvestris, Asteraceae) Leaf Extract: Phenolic Profile and Oxidative Stress Inhibitory Effects on HepG2 Cells

“…ROS levels were determined by using the 2′,7-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe [ 53 ]. Briefly, differently treated and untreated HepG2 cells (1.5 × 10 5 cells/mL) seeded in 6-well plates were incubated for 30 min with DCFH-DA (5 µM) at 37 °C.…”