Ruta graveolens L. Induces Death of Glioblastoma Cells and Neural Progenitors, but Not of Neurons, via ERK 1/2 and AKT Activation

Gao

Molecular Medicine Reports

et al. 2016

Temozolomide (TMZ) is an alkylating agent used for the treatment of aggressive forms of brain tumor based on its antitumor actions. However, the exact effect on cancer and the underlying anticancer molecular mechanism of TMZ remain to be elucidated. In the present study, the effects of TMZ on the growth and motility of glioma C6 cells were investigated. MTT and Transwell assays were used to detect cellular growth and motility. The results showed that TMZ inhibited the proliferation, migration and invasion of the glioma C6 cells in vitro, western blot analysis determined that the phosphorylation of extracellular signal‑regulated protein kinase (ERK)1/2 was decreased in the TMZ‑treated cells, compared with the untreated control cells. The ERK1/2 specific inhibitor, U0126, augmented the inhibitory effects of TMZ on the proliferation, migration and invasion of the glioma C6 cells, and the mitogen‑activated protein kinase kinase/ERK pathway activator, curcumin, attenuated the inhibitory effects of TMZ on the proliferation and motility of the glioma C6 cells. Additionally, the western blotting in the present study demonstrated that TMZ and U0126 decreased the expression of vascular endothelial growth factor-C (VEGF-C), and the expression level was restored by curcumin, suggesting that VEGF‑C may be the downstream effector of ERK1/2. Furthermore, the overexpression of VEGF‑C enhanced the growth, migration and invasion of the TMZ-treated cells. These results suggested that TMZ suppressed glioma C6 cell development, at least in part, and downregulated the expression of VEGF‑C by inhibiting the ERK signaling pathway. The results of the present study provides the foundation for a combinational therapeutic strategy to improve the efficacy of TMZ.

Section: A B C Dsupporting

confidence: 47%

Temozolomide inhibits cellular growth and motility via targeting ERK signaling in glioma C6 cells

Gao

Molecular Medicine Reports

et al. 2016

“…We also found that rue activates ERK1/2 and AKT, resulting in an inhibition of cell growth. We also show that rutin, the major component of the Ruta graveolens water extract, is unable to induce cell death [115]. Quercetin in combination with sodium butyrate promotes apoptosis in rat C6 and human T98G GBM cells by inhibiting autophagy [116].…”

Section: Quercetin Effects On Central Nervous System Cancersmentioning

confidence: 73%

Bioactive Phenolic Compounds in the Modulation of Central and Peripheral Nervous System Cancers: Facts and Misdeeds

Perrone

Sampaolo

Melone

2020

Cancers

Efficacious therapies are not available for the cure of both gliomas and glioneuronal tumors, which represent the most numerous and heterogeneous primary cancers of the central nervous system (CNS), and for neoplasms of the peripheral nervous system (PNS), which can be divided into benign tumors, mainly represented by schwannomas and neurofibromas, and malignant tumors of the peripheral nerve sheath (MPNST). Increased cellular oxidative stress and other metabolic aspects have been reported as potential etiologies in the nervous system tumors. Thus polyphenols have been tested as effective natural compounds likely useful for the prevention and therapy of this group of neoplasms, because of their antioxidant and anti-inflammatory activity. However, polyphenols show poor intestinal absorption due to individual intestinal microbiota content, poor bioavailability, and difficulty in passing the blood–brain barrier (BBB). Recently, polymeric nanoparticle-based polyphenol delivery improved their gastrointestinal absorption, their bioavailability, and entry into defined target organs. Herein, we summarize recent findings about the primary polyphenols employed for nervous system tumor prevention and treatment. We describe the limitations of their application in clinical practice and the new strategies aimed at enhancing their bioavailability and targeted delivery.

Journal Cellular Physiology

“…Our results also demonstrated that anti‐proliferative effect of rue was mediated through ERK1/2 and AKT activation. Moreover, we observed that rutin, the major component of the Ruta graveolens water extract, failed to cause cell death (Gentile et al, ).…”

Section: Chemotherapeutic Potential Of Polyphenolsmentioning

confidence: 99%

Adult‐onset brain tumors and neurodegeneration: Are polyphenols protective?

Squillaro

Schettino

Sampaolo

et al. 2017

Self Cite

Aging is a primary risk factor for both neurodegenerative disorders (NDs) and tumors such as adult-onset brain tumors. Since NDs and tumors are severe, disabling, progressive and often incurable conditions, they represent a pressing problem in terms of human suffering and economic costs to the healthcare systems. The current challenge for physicians and researchers is to develop new therapeutic strategies in both areas to improve the patients' quality of life. In addition to genetics and environmental stressors, the increase in cellular oxidative stress as one of the potential common etiologies has been reported for both disorders. Recently, the scientific community has focused on the beneficial effects of dietary antioxidant classes, known as nutraceuticals, such as carotenoids, vitamins, and polyphenols. Among these compounds, polyphenols are considered to be one of the most bioactive agents in neurodegeneration and tumor prevention. Despite the beneficial activity of polyphenols, their poor bioavailability and inefficient delivery systems are the main factors limiting their use in medicine and functional food. The development of polymeric nanoparticle-based delivery systems able to encapsulate and preserve polyphenolic compounds may represent a promising tool to enhance their stability, solubility, and cell membrane permeation. In the present review we provide an overview of the main polyphenolic compounds used for ND and brain tumor prevention and treatment that explores their mechanisms of action, recent clinical findings and principal factors limiting their application in medicine.