Polyphenols Sensitization Potentiates Susceptibility of MCF-7 and MDA MB-231 Cells to Centchroman

Polyphenols as “sensitizers” together with cytotoxic drugs as “inducers” cooperate to trigger apoptosis in various cancer cells. Hence, their combination having similar mode of mechanism may be a novel approach to enhance the efficacy of inducers. Additionally, this will also enable to achieve the physiological concentrations facilitating significant increase in the activity at concentrations which the compound can individually provide. Here we propose that polyphenols (Resveratrol (RES) and Curcumin (CUR)) pre-treatment may sensitize MCF-7/MDA MB-231 (Human Breast Cancer Cells, HBCCs) to Centchroman (CC, antineoplastic agent). 6 h pre-treated cells with 10 µM RES/CUR and 100 µM RES/30 µM CUR doses, followed by 10 µM CC for 18 h were investigated for Ser-167 ER-phosphorylation, cell cycle arrest, redox homeostasis, stress activated protein kinase (SAPKs: JNK and p38 MAPK) pathways and downstream apoptosis effectors. Low dose RES/CUR enhances the CC action through ROS mediated JNK/p38 as well as mitochondrial pathway in MCF-7 cells. However, RES/CUR sensitization enhanced apoptosis in p53 mutant MDA MB-231 cells without/with involvement of ROS mediated JNK/p38 adjunct to Caspase-9. Contrarily, through high dose sensitization in CC treated cells, the parameters remained unaltered as in polyphenols alone. We conclude that differential sensitization of HBCCs with low dose polyphenol augments apoptotic efficacy of CC. This may offer a novel approach to achieve enhanced action of CC with concomitant reduction of side effects enabling improved management of hormone-dependent breast cancer

Antioxidant and Antitumor Activity of a Bioactive Polyphenolic Fraction Isolated from the Brewing Process

There is increasing interest in identifying natural bioactive compounds that can improve mitochondrial functionality and regulate apoptosis. The brewery industry generates wastewater that could yield a natural extract containing bioactive phenolic compounds. Polyphenols act as antioxidants and have been documented to protect the human body from degenerative diseases such as cardiovascular diseases or cancer. The main aims of our research were to determine the phenolic profile of a crude extract obtained (at pilot scale) from a brewery waste stream and to evaluate the biochemical activity of this extract on the mitochondrial function of a cancer cell line (SH-SY5Y). This work is a basic translational pilot study. The total phenolic content was determined by the Folin-Ciocalteu assay, which revealed that 2.30% of the extract consisted of phenolic compounds. The polyphenols, identified and quantified by reverse-phase-high-performance liquid chromatography and mass spectrometry (RP-HPLC/MS), were mainly flavonoids. After cell culture, the tumoral cells treated with the polyphenolic extract showed enhanced mitochondrial oxidative function, which is likely related to a decrease in oxidative stress and an increase in mitochondrial biogenesis. This type of brewery waste stream, properly treated, may be a promising source of natural antioxidants to replace the synthetic antioxidants currently used in the food industry

Effect of protocatechuic acid on insulin responsiveness and inflammation in visceral adipose tissue from obese individuals: possible role for PTP1B

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Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied–despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania

Targeting the trypanosome kinetochore with CLK1 protein kinase inhibitors

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Italian garlic (Allium sativum L.) characterization through gas chromatography-isotope ratio mass spectrometry and headspace gas chromatography-mass spectrometry volatile profile

Italian garlic (Allium sativum L.) is worldwide appreciated for its unique flavour and taste. Excellence varieties such as Aglio di Voghiera and Aglio Bianco di Polesano have been officially recognised by the European Commission through the attribution of the Protected Designation of Origin (PDO) certification mark [1]. On this basis, an effective tool to preserve the reputation and the commercial value of this appreciated product, by assessing its geographical identity, is therefore required. For the first time, a method to analyse 3 volatile compounds that can be found in garlic, namely allyl alcohol (AA), triallyl disulphide (TD) and diallyl sulphide (DD), has been provided. The solid phase microextraction (SPME) followed by gas chromatography-combostiun-isotope ratio mass spectrometry (GC-C-IRMS) successfully lead to the analysis of the carbon isotopic ratios (δ13C) of the mentioned compounds. To ensure the repeatability of the method, a chosen sample has been analysed 10 consecutive times and also in different days. Moreover, the quantification of the volatile compounds was carried out through gas chromatography-mass spectrometry (GC-MS/MS). To first apply both methods, a set made up of 32 red garlic samples coming from 3 different Italian regions (Abruzzo, Lazio and Sicily) has been considered. Higher relative amounts of DD and DT were found in Sicilian samples with respect to Lazio and Abruzzo ones. Although to date no statistical differences could be found among the δ13CAA, δ13CDT and δ13CDD of the three groups, it must be considered the low number of samples, that has to be widened to verify whether the method could make it possible to discriminate among different regions. Moreover, garlic samples belonging to foreign competitors should be considered to look for differences in the δ13C of AA, DT and DD and more volatile compounds could be included in the analysi