Rutin (Bioflavonoid) as Cell Signaling Pathway Modulator: Prospects in Treatment and Chemoprevention.

Cancer is a complex ailment orchestrated by numerous intrinsic and extrinsic pathways. Recent research has displayed a deep interest in developing plant-based cancer therapeutics for better management of the disease and limited side effects. A wide range of plant-derived compounds have been reported for their anticancer potential in the quest of finding an effective therapeutic approach. Rutin (vitamin P) is a low-molecular weight flavonoid glycoside (polyphenolic compound), abundantly present in various vegetables, fruits (especially berries and citrus fruits), and medicinal herbs. Numerous studies have delineated several pharmacological properties of rutin such as its antiprotozoal, antibacterial, anti-inflammatory, antitumor, antiviral, antiallergic, vasoactive, cytoprotective, antispasmodic, hypolipidemic, antihypertensive, and antiplatelet properties. Specifically, rutin-mediated anticancerous activities have been reported in several cancerous cell lines, but the most common scientific evidence, encompassing several molecular processes and interactions, including apoptosis pathway regulation, aberrant cell signaling pathways, and oncogenic genes, has not been thoroughly studied. In this direction, we attempted to project rutin-mediated oncogenic pathway regulation in various carcinomas. Additionally, we also incorporated advanced research that has uncovered the notable potential of rutin in the modulation of several key cellular functions via interaction with mRNAs, with major emphasis on elucidating direct miRNA targets of rutin as well as the process needed to transform these approaches for developing novel therapeutic interventions for the treatment of several cancers.

Fatty acid synthesis by Chlamydomonas reinhardtii in phosphorus limitation.

The importance of crucial nutrient factors like Phosphate (P) and their limited availability leads to variable fluctuations in fatty acid and phospholipid synthesis in the green alga. These fatty acids and phospholipids are an imperative byproduct of alga which used in biofuel production. The production of phospholipids in alga might be naturally enhanced by the optimized supplied by specific essential nutrient like Phosphate. In this study, green alga Chlamydomonas reinhardtii was cultivated in phosphate stress condition to obtain maximum phospholipids. In the stress condition, the organism exhibited variable changes in chlorophyll, fatty acid, and phospholipid compositions. These parameters analyzed by biomass, X-ray, GC, and TLC. Remarkably, saturated fatty acids, monounsaturated, and di-unsaturated fatty acids amounts, increases, while polyunsaturated fatty acids to decrease markedly. The maximum fatty acid content observed at 0.4 mgl-1 P content in growing media. A broad peak area of 56% of hexadecanoic acid (C 16:0) and followed by 28.8% linolenic (C18:3) was observed in GC analysis. These results indicate the essential fatty acid accumulation maximized at particular phosphate concentration in growing media. This necessary and essential fatty acid production from green algae in a sustainable manner is an inexpensive and excellent way for commercialization and biofuel production.

Bougainvillea flower extract mediated zinc oxide's nanomaterials for antimicrobial and anticancer activity.

The zinc oxide nanomaterials (ZnO-NMs), owing to their broad biomedical applications have lately attracted the incredible interest in the development of therapeutic agents against microbial infections. In this contribution, we have biosynthesized ZnO-NMs with a size of ˜ 40 nm from the Bougainvillea flower extracts. The FTIR and SEM-EDX mapping analysis confirmed the size, shape and biogenic origin of ZnO-NPs. Furthermore, the purified ZnO-NMs were applied for antibacterial studies against susceptible and resistant bacterial strains and to elucidate the possible mechanism of their activity. The XTT assay and confocal imaging confirmed the ZnO-NMs materials anti-biofilm activities against medically important pathogens, i.e., S. aureus and E. coli. Moreover, the absence of cytotoxicity against healthy kidney cells (HEK-293) and erythrocytes confirmed their biocompatible nature. Furthermore, the biosynthesized ZnO-NMs showed potent anticancer activity against the breast cancer cell line (MCF-7). These biosynthesized ZnO-NMs are having excellent antimicrobial and anticancer activities and are highly biocompatible due to biogenic nature. During antimicrobial study, Zno-NMs showed excellent minimum inhibitory concentration 16 µg concentration againt E. coli, P. aeruginosa and S. aureus. While in anticancer activity, of ZnO-NMs with 15 µg/ml dose showed good response against MCF-7 cell line. Further, this killing was mechanically confirmed by ROS generation by the ZnO-NMs, which cause cell lysis by the peroxidation of membrane lipid. So, this biogenic ZnO-NMs can be used in the future for nanomaterial-based drug development.

Effect of Diets, Familial History, and Alternative Therapies on Genomic Instability of Breast Cancer Patients.

This study evaluates a correlation between family history, micronutrients intake, and alternative therapies with genetic instability, before and during breast cancer treatment. For this study, a total of 150 women were selected. Among those, 50 women were breast cancer patients on chemotherapy, while 50 breast cancer patients were on radiotherapy, and 50 were healthy females. All the participants signed the informed consent form and answered the public health questionnaire. Samples of buccal epithelial and peripheral blood cells were collected and analyzed through micronucleus and comet assays. The cells were evaluated for apoptosis and DNA damage. Results showed the association of patients' family history with an increase in toxicogenetic damage before and during cancer therapy. On the other hand, patients with late-onset cancer also presented genetic instability before and during therapy, along with those who did not take sufficient vegetables and alternative therapies. A positive correlation was observed between the genetic instability and alternative therapies, while inverse correlation was recorded with the vegetable consumption. Results clearly explain that the nutritional aspects and alternative therapies influence the genetic instability before and during cancer therapies especially in radiotherapy treated patients. Our data could be used for the monitoring therapies and management of breast cancer patients.

Antimicrobial and anticancer activities of silver nanoparticles synthesized from the root hair extract of Phoenix dactylifera.

There is a continuous rise in the rate of medicine consumption because of the development of drug resistance by microbial pathogens. In the last one decade, silver nanoparticles (AgNPs) have become a remarkable choice for the development of new drugs due to their excellent broad-spectrum antimicrobial activity. In the current piece of work, we have synthesized AgNPs from the root extract of Phoenix dactylifera to test their antimicrobial and anti-cancer potential. UV-visible spectra showed the surface plasmon resonance peak at 420 nm λmax corresponding to the formation of silver nanoparticles, FTIR spectra further confirmed the involvement of biological moieties in AgNPs synthesis. Moreover, XRD analysis showed the crystalline nature of AgNPs and predicted the crystallite size of 15 to 40 nm. Electron microscopy analyses confirmed their spherical shape. In addition, synthesized AgNPs was also found to control the growth of C. albicans and E. coli on solid nutrient medium with 20 and 22 mm zone of inhibition, respectively. The 100% potency at 40 µg/ml AgNPs concentration was observed against E. coli and C. albicans after 4 h and 48 h incubation respectively. Importantly, AgNPs were also found to decrease the cell viability of MCF7 cell lines in vitro with IC50 values of 29.6 µg/ml and could act as a controlling agent of human breast cancer. Based on our results, we conclude that biologically synthesized AgNPs exhibited multifunctional properties and could be used against human cancer and other infectious diseases.

Mobilization of Nuclear Copper by Green Tea Polyphenol Epicatechin-3-Gallate and Subsequent Prooxidant Breakage of Cellular DNA: Implications for Cancer Chemotherapy.

Epidemiological as well as experimental evidence exists in support of chemopreventive and anticancer properties of green tea and its constituents. The gallocatechin, epicatechin-3-gallate is a major polyphenol present in green tea, shown responsible for these effects. Plant-derived polyphenolic compounds are established natural antioxidants which are capable of catalyzing oxidative DNA degradation of cellular DNA, alone as well as in the presence of transition metal ions, such as copper. Here we present evidence to support that, similar to various other polyphenoic compounds, epicatechin-3-gallate also causes oxidative degradation of cellular DNA. Single cell alkaline gel electrophoresis (Comet assay) was used to assess DNA breakage in lymphocytes that were exposed to various concentrations of epicatechin-3-gallate. Inhibition of DNA breakage in the presence of scavengers of reactive oxygen species (ROS) suggested involvement of ROS generation. Addition of neocuproine (a cell membrane permeable Cu(I) chelator) inhibited DNA degradation, dose-dependently, in intact lymphocytes. In contrast, bathocuproine, which does not permeate cell membrane, was observed to be ineffective. We further show that epicatechin-3-gallate degrades DNA in cell nuclei, which can also be inhibited by neocuproine, suggesting mobilization of nuclear copper in this reaction as well. Our results are indicative of ROS generation, possibly through mobilization of endogenous copper ions, and support our long-standing hypothesis of a prooxidant activity of plant-derived polyphenols as a mechanism for their documented anticancer properties.

Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen species.

Catechins, the dietary phytochemicals present in green tea and other beverages, are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. While it is believed that the antioxidant properties of catechins and related dietary agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, these properties cannot account for apoptosis induction and chemotherapeutic observations. Catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) are the four major constituents of green tea. In this article, using human peripheral lymphocytes and comet assay, we show that C, EC, EGC and EGCG cause cellular DNA breakage and can alternatively switch to a prooxidant action in the presence of transition metals such as copper. The cellular DNA breakage was found to be significantly enhanced in the presence of copper ions. Catechins were found to be effective in providing protection against oxidative stress induced by tertbutylhydroperoxide, as measured by oxidative DNA breakage in lymphocytes. The prooxidant action of catechins involved production of hydroxyl radicals through redox recycling of copper ions. We also determined that catechins, particularly EGCG, inhibit proliferation of breast cancer cell line MDA-MB-231 leading to a prooxidant cell death. Since it is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies, cancer cells would be more subject to redox cycling between copper ions and catechins to generate reactive oxygen species (ROS) responsible for DNA breakage. Such a copper dependent prooxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells.

Bacteria and fungi can contribute to nutrients bioavailability and aggregate formation in degraded soils.

Intensive agricultural practices and cultivation of exhaustive crops has deteriorated soil fertility and its quality in agroecosystems. According to an estimate, such practices will convert 30% of the total world cultivated soil into degraded land by 2020. Soil structure and fertility loss are one of the main causes of soil degradation. They are also considered as a major threat to crop production and food security for future generations. Implementing safe and environmental friendly technology would be viable solution for achieving sustainable restoration of degraded soils. Bacterial and fungal inocula have a potential to reinstate the fertility of degraded land through various processes. These microorganisms increase the nutrient bioavailability through nitrogen fixation and mobilization of key nutrients (phosphorus, potassium and iron) to the crop plants while remediate soil structure by improving its aggregation and stability. Success rate of such inocula under field conditions depends on their antagonistic or synergistic interaction with indigenous microbes or their inoculation with organic fertilizers. Co-inoculation of bacteria and fungi with or without organic fertilizer are more beneficial for reinstating the soil fertility and organic matter content than single inoculum. Such factors are of great importance when considering bacteria and fungi inocula for restoration of degraded soils. The overview of presented mechanisms and interactions will help agriculturists in planning sustainable management strategy for reinstating the fertility of degraded soil and assist them in reducing the negative impact of artificial fertilizers on our environment.

Physico-chemical stress induced amyloid formation in insulin: Amyloid characterization, cytotoxicity analysis against human neuroblastoma cell lines and its prevention using black seeds (Nigella sativa).

OBJECTIVE: To investigate the aggregation and fibrillation of insulin at low pH and moderate temperature; and to further test the aggregated insulin for its cytotoxicity on human neuroblastoma (SH-SY5Y) cell line and inhibition of the cytotoxicity by black seeds (Nigella sativa) extract. METHODS: Bovine pancreatic insulin was incubated at pH 2.0, 45 ℃ under stirring condition at 400 r/min for 24 h. Amyloids like structures in the aggregated insulin were characterized using various techniques such as thioflavin T assay (ThT), 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence, circular dichroism (CD) and dynamic light scattering (DLS). Moreover, cytotoxicity of aggregated insulin was monitored on SH-SY5Y cell line in the presence and absence of black seeds extract using standard 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and reactive oxygen species (ROS) assay kit. RESULTS: Our finding demonstrated that insulin under the mentioned conditions formed amyloid-like structure. ANS binding to aggregated insulin showed increase in fluorescence, suggesting structural change and increase in hydrophobicity in insulin occurring during the fibril formation. DLS measurement revealed progressive increase in hydrodynamic radius of aggregated insulin. Cytotoxicity assays illustrated aggregated insulin induced apoptosis in SH-SY5Y cell through ROS formation. Moreover, LDH measurement showed aggregated insulin triggered membrane damage in SH-SY5Y cell lines. Black seeds extract was found to inhibit amyloid formation and protected the cells against amyloid toxicity. CONCLUSION: Insulin molded into amyloid like structure at low pH and under stirring conditions. Characterization of insulin aggregates illustrated conformational change in insulin and it experiences α-helix to ß-sheet transition during the course of fibrillation. Black seeds extract inhibited amyloid progression of insulin via ROS scavenging and restrained the cytotoxicity caused by insulin fibrils suggesting black seeds containing polyphenols may serve as a lead structure to a novel anti-amyloidogenic drugs.