Search results for "autophagy"

p8 (candidate of metasiasis 1) drives ER-stress/autophagy/apoptosis axis induced by the synthetic cannabinoid WIN in HCC cells.

2010

Background: Today, evidence is emerging for the role of autophagy in the regulation of life and death of tumour cells and its relationship with ER-stress signaling. Our previous results demonstrated that hepatoma HepG2 cells are sensitive to apoptotic effects induced by WIN, a synthetic cannabinoid, which acts through a mechanism involving the reduction in the levels of some survival factors and the activation of pro-apoptotic ones. Since WIN effects were observed after 36−48 hours of treatment, we investigated the possible activation of ER-stress and autophagic process in the first hours of WIN treatment focusing our attention on p8, a factor whose expression is upregulated in response to …

Methylation decrease of BECN1 gene induced by phytochemical Indicaxantin in Caco2 cells: an epigenetic hypothesis of autophagy

2014

Autophagy is a highly conserved catabolic process that degrades and recycles intracellular components through the lysosomes [1]. The role of this process in tumorigenesis and tumor progression is controversial: in the early stages, it can block tumor growth and conversely it can promote its progression in the later stages [2]. The tumor suppressor BECN1 gene, encodes the protein Beclin 1, a marker of autophagy down-regulated in several types of cancer, such as colorectal cancer [3]. There are a lot of both genetic and environmental risk factors for colorectal cancer, including diet: for this reason, in accordance with epidemiological studies, consumption of foods rich in phytochemicals is w…

METHYLOMIC SIGNATURE AND MOLECULAR MODELLING TO BETTER UNDERSTAND AUTOPHAGY INDUCED BY PHYTOCHEMICAL IN CACO-2 CELLS

2019

The binomial “autophagy-cancer” is intricate and methylomic studies can help to understand it by changing point of view from a gene level to an -omic one. Recently, autophagy-modulating properties of several phytochemicals have attracted attention in anticancer research. We evaluated whether Indicaxanthin (IND), the peculiar known beneficial phytochemical of prickly pear, seasonally available in the southern Italy, could induce autophagy in Caco2 cells, and whether it results from an epigenomic modification and/or a direct molecular interaction. IND increased autophagy in Caco-2 cells; the methylomic signature, obtained by Reduced Representation Bisulfite Sequencing (15 million of clusters)…

Nutritional prevention of cognitive decline and dementia.

2018

Cognitive impairment results from a complex interplay of many factors. The most important independent predictor of cognitive decline is age but other contributing factors include demographic, genetic, socio-economic, and environmental parameters, including nutrition. The number of persons with cognitive decline and dementia will increase in the next decades in parallel with aging of the world population. Effective pharmaceutical treatments for age-related cognitive decline are lacking, emphasizing the importance of prevention strategies. There is extensive evidence supporting a relationship between diet and cognitive functions. Thus, nutritional approaches to prevent or slow cognitive decli…

Asimmetric skeleton patterns induced by gadolinium ions in sea urchin embryos: focus on mechanisms regulating skeletogenesis and comparison among phy…

2014

The NUPR1/p73 axis contributes to sorafenib resistance in hepatocellular carcinoma

2021

The multikinase inhibitor sorafenib was the first drug approved by the FDA for treating patients with advanced hepatocellular carcinoma (HCC). However, sorafenib resistance remains a major challenge for improving the effectiveness of HCC treatment. Previously, we identified several genes modulated after sorafenib treatment of human HCC cells, including the stress-inducible nuclear protein 1 (NUPR1) gene. Multiple studies have shown that NUPR1 regulates autophagy, apoptosis, and chemoresistance. Here, we demonstrate that treatment of HCC cells with sorafenib resulted in the activation of autophagic flux. NUPR1 knock-down (KD) in HCC cells was associated with increased p62 expression, suggest…

New complex polycyclic compounds: Synthesis, antiproliferative activity and mechanism of action

2020

Abstract Polycyclic or O-glycoconiugate polycyclic compounds 1a-g were previously tested for their in vitro antiproliferative activity. In this series of compounds, activity increases as log P decreases. Specifically, compounds 1d and 1g showed lower log P values together with the best antiproliferative profiles. With the aim of extending our understanding of the structure–activity relationship (SAR) of this class of compounds, we prepared new polycyclic derivatives 2a-c, which bear on each of the two phenyl rings hydrophilic substituents (OH, SO2NH2 or NHCOCH3). These substituents are able to form hydrogen bonds and to decrease the partition coefficient value as compared with compound 1d. …

2-Hydroxyoleic Acid Induces ER Stress and Autophagy in Various Human Glioma Cell Lines

2012

Background: 2-Hydroxyoleic acid is a synthetic fatty acid with potent anti-cancer activity which does not induce undesired side effects. However, the molecular and cellular mechanisms by which this compound selectively kills human glioma cancer cells without killing normal cells is not fully understood. The present study was designed to determine the molecular bases underlying the potency against 1321N1, SF-767 and U118 human glioma cell lines growth without affecting non cancer MRC-5 cells. Methodology/Principal Findings: The cellular levels of endoplasmic reticulum (ER) stress, unfolded protein response (UPR) and autophagy markers were determined by quantitative RT-PCR and immunoblotting …

Ultrastructural changes of sparkling wine lees during long-term aging in real enological conditions.

2012

Ultrastructural changes of lees of three series of sparkling wines produced using the traditional method during long-term aging (4 years) were assessed by high-pressure freezing in combination with transmission electron microscopy. The stratified structure of the cell wall disappeared throughout aging. After 18 months, the microfibrous material of the cell wall appeared more diffuse and the amorphous midzone of the inner wall layer was progressively degraded. From 30 months onward, the cell wall consisted of a tangled structure of fibers. In spite of these changes, the cell wall of yeasts remained unbroken at 48 months of wine aging. Cell membrane breakage was observed for the first time in…

mTOR Driven Gene Transcription Is Required for Cholesterol Production in Neurons of the Developing Cerebral Cortex

2021

AbstractDysregulated mammalian target of rapamycin (mTOR) activity is associated with various neurodevelopmental disorders ranging from idiopathic autism spectrum disorders to syndromes caused by single gene defects. This suggests that maintaining mTOR activity levels in a physiological range is essential for brain development and functioning. Upon activation, mTOR regulates a variety of cellular processes such as cell growth, autophagy and metabolism. On a molecular level, however, the consequences of mTOR activation in the brain are not well understood.Low levels of cholesterol are associated with a wide variety of neurodevelopmental disorders. We here describe numerous genes of the stero…