showing 23 related works from this author
Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcino…
2015
Abstract The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv), against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter prevented acute UVB (360 mJ/cm2)-induced increase in skin fold, thickness, and redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter, but not Resv, effectively prevented chronic UVB (180 mJ/cm2, three doses/week for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not develop skin carcinomas, whereas a large number of tumors were observed in all controls). This anticarcinogenic effect was associated wit…
Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane permeabilization-dependent mechanism.
2012
The phenolic phytoalexin resveratrol is well known for its health-promoting and anticancer properties. Its potential benefits are, however, limited due to its low bioavailability. Pterostilbene, a natural dimethoxylated analog of resveratrol, presents higher anticancer activity than resveratrol. The mechanisms by which this polyphenol acts against cancer cells are, however, unclear. Here, we show that pterostilbene effectively inhibits cancer cell growth and stimulates apoptosis and autophagosome accumulation in cancer cells of various origins. However, these mechanisms are not determinant in cell demise. Pterostilbene promotes cancer cell death via a mechanism involving lysosomal membrane …
Polyphenolic Phytochemicals in Cancer Prevention and Therapy: Bioavailability versus Bioefficacy
2017
Natural polyphenols are organic chemicals which contain phenol units in their structures. They show antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Still, definitively demonstrating the human benefits of isolated polyphenolic compounds (alone or in combination) using modern scientific methodology has proved challenging. The most common discrepancy between experimental and clinical observations is the use of nonphysiologically relevant concentrations of polyphenols in mechanistic studies. Thus, it remains highly controversial how applicable underlying mechanisms are with bioavailable concentrations and biological half-li…
Abstract 4239: Pterostilbene, a natural polyphenol, elicits full protection against ultraviolet B radiation-induced skin carcinogenesis: Preclinical …
2011
Abstract Solar radiation exposure is the chief cause of nonmelanoma (i e, basal cell and squamous cell) skin cancer, and it is also a prime factor in the etiology of cutaneous melanoma The cancer-causing effects of ultraviolet (UV) radiation on the skin are mainly produced by UV-B radiation in the 290- to 320-nm range, the same range that produces burning in human skin (erythema) UV-B exposure can damage DNA and be immunosuppressive Thus, and considering the alarming numbers of skin cancers being diagnosed around the world, it is increasingly evident the need of effective protection from UV radiation Resveratrol (trans-3,5,4′-trihydroxystilbene; RES) is a phytoalexin present in a wide varie…
Role of Natural Stilbenes in the Prevention of Cancer
2015
Natural stilbenes are an important group of nonflavonoid phytochemicals of polyphenolic structure characterized by the presence of a 1,2-diphenylethylene nucleus. Stilbenes have an extraordinary potential for the prevention and treatment of different diseases, including cancer, due to their antioxidant, cell death activation, and anti-inflammatory properties which associate with low toxicity underin vivoconditions. This review aims to discuss various approaches related to their mechanisms of action, pharmacological activities in animal models and humans, and potential chemoprevention in clinical studies. The biological activity of natural stilbenes is still incompletely understood. Furtherm…
Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload
2017
Abstract Objective To assess the generation of reactive oxygen species (ROS) and the involvement of the main antioxidant pathways in low/intermediate-1-risk myelodysplastic syndromes (MDS) with iron overload (IOL). Methods We examined the levels of superoxide anion (O2 −), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (ΔΨm), and by-products of oxidative damage (8-isoprostanes and 8-oxo-7,8-dihydro-2′-deoxyguanosine, 8-oxo-dG) in 42 MDS patients (28 without IOL at diagnosis, and 14 who developed IOL) and 20 healthy subjects. Results Patients with IOL showed higher O2 − lev…
Abstract LB-099: Metabolic vulnerabilities of mesenchymal-like EGFR-mutant NSCLC cells with acquired resistance to tyrosine kinase inhibitors
2018
Abstract Despite the availability of the effective targeted therapies in lung cancer, such as EGFR tyrosine kinase inhibitors (TKIs), drug tolerance and acquired resistance are two common problems that negatively impact lung cancer patient survival. Consequently it is important to understand the molecular basis of the drug tolerance and resistance so that we could formulate effective strategies to ameliorate the efficacy of existing drug and to suppress the emergence of drug resistance. A burgeoning body of literature demonstrated that epigenetic changes by the methylation of DNA and histones are critical in acquired drug resistance, especially in those cancer cells with stem cell-like prop…
Glutathione in metastases: From mechanisms to clinical applications.
2016
Metastatic spread, not primary tumors, is the leading cause of cancer death. Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is particularly relevant in cancer cells as it is involved in regulating carcinogenic mechanisms, growth and dissemination, and multidrug and radiation resistance. Upon interaction of metastatic cells with the vascular endothelium, a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium. GSH release from different organs, mainly the liver, and its interorgan transport through the blood circulation to metastatic foci, promote their growth. This review focuses on the relation…
Abstract 753: Genomic alterations of autophagy genes disrupts autophagic flux in human lung adenocarcinomas
2015
Abstract Targeted therapy using EGFR tyrosine kinase inhibitor (TKI) is a standard therapy for a subset of non-small cell lung cancer (NSCLC) patients with lung adenocarcinomas (LADs) harboring EGFR kinase domain mutations; however, EGFR TKI therapy shows limited efficacy due to de novo and acquired resistance. Consequently, formulating strategies to potentiate the efficacy of EGFR TKI is of great interest. In EGFR TKI sensitive cells harboring EGFR mutation, it has been shown that EGFR inhibition induces autophagy to protect the cells from metabolic stress. Hydroxychloroquine (HQ), an inhibitor of autophagy, has been shown to potentiate EGFR TKIs in preclinical models, however, preliminary…
Bcl-2 and Mn-SOD antisense oligodeoxynucleotides and a glutamine-enriched diet facilitate elimination of highly resistant B16 melanoma cells by tumor…
2005
Mitochondrial glutathione (mtGSH) depletion increases sensitivity of Bcl-2-overexpressing B16 melanoma (B16M)-F10 cells (high metastatic potential) to tumor necrosis factor-alpha (TNF-alpha)-induced oxidative stress and death in vitro. In vivo, mtGSH depletion in B16M-F10 cells was achieved by feeding mice (where the B16M-F10 grew as a solid tumor in the footpad) with an L-glutamine (L-Gln)-enriched diet, which promoted in the tumor cells an increase in glutaminase activity, accumulation of cytosolic L-glutamate, and competitive inhibition of GSH transport into mitochondria. L-Gln-adapted B16M-F10 cells, isolated using anti-Met-72 monoclonal antibodies and flow cytometry-coupled cell sortin…
Pterostilbene: Biomedical applications
2013
Resveratrol and its naturally dimethylated analog, pterostilbene, show similar biological activities. However, the higher in vivo bioavailability of pterostilbene represents a fundamental advantage. The main focus of this review is on biomedical applications of pterostilbene. The metabolism and pharmacokinetics of this stilbene in inflammatory dermatoses and photoprotection, cancer prevention and therapy, insulin sensitivity, blood glycemia and lipid levels, cardiovascular diseases, aging, and memory and cognition are addressed. Safety and toxicity, as well as recommendations for future research and biomedical uses, are discussed. This review includes comparisons between pterostilbene and o…
Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism
2013
[EN] Background: Interleukin (IL)-6 (mainly of tumor origin) activates glutathione (GSH) release from hepatocytes and its interorgan transport to B16-F10 melanoma metastatic foci. We studied if this capacity to overproduce IL-6 is regulated by cancer cell-independent mechanisms. Methods: Murine B16-F10 melanoma cells were cultured, transfected with red fluorescent protein, injected i.v. into syngenic C57BL/6J mice to generate lung and liver metastases, and isolated from metastatic foci using high-performance cell sorting. Stress hormones and IL-6 levels were measured by ELISA, and CRH expression in the brain by in situ hybridization. DNA binding activity of NF-kappa B, CREB, AP-1, and NF-IL…
Natural polyphenols in cancer therapy.
2011
Natural polyphenols are secondary metabolites of plants involved in defense against different types of stress. Extracts containing these compounds have been used for thousands of years in traditional eastern medicine. Polyphenols act on multiple targets in pathways and mechanisms related to carcinogenesis, tumor cell proliferation and death, inflammation, metastatic spread, angiogenesis, or drug and radiation resistance. Nevertheless, reported effects claimed for polyphenols are controversial, since correlations between in vitro effects and in vivo evidence are poorly established. The main discrepancy between health claims versus clinical observations is the frequent use of nonphysiological…
Nitric Oxide Mediates Natural Polyphenol-induced Bcl-2 Down-regulation and Activation of Cell Death in Metastatic B16 Melanoma
2007
Intravenous administration to mice of trans-pterostilbene (t-PTER; 3,5-dimethoxy-4'-hydroxystilbene) and quercetin (QUER; 3,3',4',5,6-pentahydroxyflavone), two structurally related and naturally occurring small polyphenols, inhibits metastatic growth of highly malignant B16 melanoma F10 (B16M-F10) cells. t-PTER and QUER inhibit bcl-2 expression in metastatic cells, which sensitizes them to vascular endothelium-induced cytotoxicity. However, the molecular mechanism(s) linking polyphenol signaling and bcl-2 expression are unknown. NO is a potential bioregulator of apoptosis with controversial effects on Bcl-2 regulation. Polyphenols may affect NO generation. Short-term exposure (60 min/day) t…
Abstract 4219: Lysosomal membrane permeabilization, a novel anticancer mechanism induced by pterostilbene
2011
Abstract Pterostilbene (Pter) (3,5-dimethoxy-4′-hydroxystilbene), a natural dimethylated analog of resveratrol, is a phytoalexin abundant in plants and fruits with a number of potential benefits for human health. Darakchasava, an Indian herbal preparation of Vitis Vinifera, contains Pter and is prescribed as a cardiotonic in ayurvedic and traditional medicine. Furthermore, some observations indicate that Pter can be beneficial in the prevention and treatment of different diseases such as diabetes, dyslipidemia, or cancer. Pter shows higher bioavailability than resveratrol. The substitution of two OH groups (positions 3 and 5) by methyl groups increases the stabilityof the molecule and its r…
Temporal molecular and biological assessment of an erlotinib-resistant lung adenocarcinoma model reveals markers of tumor progression and treatment r…
2012
Abstract Patients with lung cancer with activating mutations in the EGF receptor (EGFR) kinase, who are treated long-term with tyrosine kinase inhibitors (TKI), often develop secondary mutations in EGFR associated with resistance. Mice engineered to develop lung adenocarcinomas driven by the human EGFR T790M resistance mutation are similarly resistant to the EGFR TKI erlotinib. By tumor volume endpoint analysis, these mouse tumors respond to BIBW 2992 (an irreversible EGFR/HER2 TKI) and rapamycin combination therapy. To correlate EGFR-driven changes in the lung with response to drug treatment, we conducted an integrative analysis of global transcriptome and metabolite profiling compared wit…
Oxidative stress in environmental-induced carcinogenesis.
2009
Reactive oxygen species (ROS) are the more abundant free radicals in nature and have been related with a number of tissue/organ injuries induced by xenobiotics, ischemia, activation of leucocytes, UV exposition, etc. Oxidative stress is caused by an imbalance between ROS production and a biological system's ability to readily detoxify these reactive intermediates or easily repair the resulting damage. Thus, oxidative stress is accepted as a critical pathophysiological mechanism in different frequent human pathologies, including cancer. In fact ROS can cause protein, lipid, and DNA damage, and malignant tumors often show increased levels of DNA base oxidation and mutations. Different lifesty…
Oxidative and nitrosative stress in the metastatic microenvironment.
2010
Metastases that are resistant to conventional therapies are the main cause of most cancer-related deaths in humans. Tumor cell heterogeneity, which associates with genomic and phenotypic instability, represents a major problem for cancer therapy. Additional factors, such as the attack of immune cells or organ-specific microenvironments, also influence metastatic cell behavior and the response to therapy. Interaction of cancer and endothelial cells in capillary beds, involving mechanical contact and transient adhesion, is a critical step in the initiation of metastasis. This interaction initiates a cascade of activation pathways that involves cytokines, growth factors, bioactive lipids and r…
Abstract 1280: Pterostilbene exerts full protection against UVB-induced skin carcinogenesis.
2013
Abstract Epidemiological, clinical and laboratory studies have demonstrated that solar ultraviolet (UV) radiation is the main cause of nonmelanoma skin cancer (i.e., basal cell and squamous cell carcinoma) and it is also a prime factor in the etiology of cutaneous melanoma. The cancer-causing effects of solar exposure on the skin are mainly produced by UV-B radiation in the 290- to 320-nm range, the same range that produces burning in human skin (erythema), inflammation, oxidative stress, DNA damage, etc. Thus, and considering the alarming numbers of skin cancers being diagnosed around the world, it is increasingly evident the need of an effective protection against UV radiation. Polyphenol…
Bcl-2 and glutathione depletion sensitizes B16 melanoma to combination therapy and eliminates metastatic disease.
2007
Abstract Purpose: Advanced melanoma resists all current therapies, and metastases in the liver are particularly problematic. Prevalent resistance factors include elevated glutathione (GSH) and increased expression of bcl-2 in melanoma cells. GSH has pleiotropic effects promoting cell growth and broad resistance to therapy, whereas Bcl-2 inhibits the activation of apoptosis and contributes to elevation of GSH. This study determined the in vivo efficacy of combination therapies administered while GSH and Bcl-2 were individually and simultaneously decreased in metastatic melanoma lesions. Experimental Design: Highly metastatic murine B16 melanoma (B16M-F10) cells have elevated levels of both G…
Glutathione in Cancer Cell Death
2011
Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and…
Nitric Oxide: A Rate-Limiting Factor for Metastases Development
2010
Genomic and phenotypic instability associates with cancer cell heterogeneity. Although it has been argued that metastatic/invasive phenotypes are already present in primary tumors, highly aggressive and resistant cancer cell subsets may develop during in vivo growth and/or as a consequence of therapy. Moreover, factors such as the attack of our immune system or organ-specific microenvironments also affect cancer cell behavior and the subsequent response to drugs and/or other therapeutic agents. Interaction of cancer and endothelial cells in capillary beds initiates a cascade of molecular events that involve cytokines, growth factors, bioactive lipids, and reactive nitrogen and oxygen specie…
Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: a Bcl-2- and superoxide dismutase 2-dependent …
2008
AbstractColorectal cancer is one of the most common malignancies worldwide. The treatment of advanced colorectal cancer with chemotherapy and radiation has two major problems: development of tumor resistance to therapy and nonspecific toxicity towards normal tissues. Different plant-derived polyphenols show anticancer properties and are pharmacologically safe. In vitro growth of human HT-29 colorectal cancer cells is inhibited (∼56%) by bioavailable concentrations of trans-pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene; t-PTER) and quercetin (3,3′,4′,5,6-pentahydroxyflavone; QUER), two structurally related and naturally occurring small polyphenols. I.v. administration of t-PTER and Q…