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Cancer traits dependent chemo and radiotherapy display acute toxicity and long-term side effects. Since last two decades, researchers investigated a new anticancer agents derived from plants. Cassia alata (L.) is a medicinal herb distributed in the tropical and humid regions. In this study, C. alata flower methanol extract (CME) have been prepared using cold percolation method and the phytochemical components were identified using GC–MS analysis. CME have been used to study the antiproliferative and apoptosis properties against human colon cancer HT-115 colon cancer cells, its molecular mechanism have been explored. 0.2 mg/mL dose of CME, inhibited 50% of HT-115 colon cancer cell growth after 48hr was confirmed the significant antiproliferation effect. In normal cells such as Vero cells and hMSCs, 0.2 mg/mL dose of CME shown only 4% and 5% growth inhibition confirmed the HT-115 cell specific cytotoxic effect. This effect might be due to the availability of phytoactive biomolecules in CME such as, cyclotrisiloxan, beta-sitosterol and alpha-tocopherol have been confirmed by GC–MS. Most interestingly, PI and AO/ErBr staining of CME treated HT-115 cells shown early (25%), pro (17%) and late (8%) apoptotic and 3% necrotic cells after 48 hr. Treatment with CME extract showed potential effect on the inhibition of protumorigenic inflammatory and oxidative stress genes. Protumorigenic COX-2/PGE-2 and TNF-α/NF-κB immune axis were normalized after CME treatment. Amounts of both apoptosis related mRNA p53, Bax, caspase 3 and p21 genes were upregulated, whereas it resulted in significant reduction in the anti-apoptotic marker mdm2 and Bcl-2 genes. In conclusion, bioactive compounds present in CME potentially inhibit HT-115 colon cancer cell proliferation via an inhibition of protumorigenic immune axis and stimulation of mitochondria dependent apoptotic pathway without necrotic effect.

Salinity and drought are the major abiotic stresses that disturb several aspects of maize plants growth at the cellular level, one of these aspects is cell cycle machinery. In our study, we dissected the molecular alterations and downstream effectors of salinity and drought stress on cell cycle regulation and chromatin remodeling. Effects of salinity and drought stress were determined on maize seedlings using 200 mM NaCl (induced salinity stress), and 250 mM mannitol (induced drought stress) treatments, then cell cycle progression and chromatin remodeling dynamics were investigated. Seedlings displayed severe growth defects, including inhibition of root growth. Interestingly, stress treatments induced cell cycle arrest in S-phase with extensive depletion of cyclins B1 and A1. Further investigation of gene expression profiles of cell cycle regulators showed the downregulation of the CDKA, CDKB, CYCA, and CYCB. These results reveal the direct link between salinity and drought stress and cell cycle deregulation leading to a low cell proliferation rate. Moreover, abiotic stress alters chromatin remodeling dynamic in a way that directs the cell cycle arrest. We observed low DNA methylation patterns accompanied by dynamic histone modifications that favor chromatin decondensation. Also, the high expression of DNA topoisomerase 2, 6 family was detected as consequence of DNA damage. In conclusion, in response to salinity and drought stress, maize seedlings exhibit modulation of cell cycle progression, resulting in the cell cycle arrest through chromatin remodeling.

A pot experiment was carried out to study the effects of NPK and Actosol on plant growth , essential oil , chemical composition and antioxidant activity of Zanthoxylum piperitum plant, it was conducted under in saran greenhouse, at the Experimental Nursery of the Ornamental Horticulture Depart., Fac., of Agric. ,Cairo Univ., during 2018/2019- 2019/2020.The plants were fertilized with NPK at 12g/plant (100% recommended dose), 9 and 6 g/ plant ,sprayed with Actosol at 0, 1.5 and 2.5 ml/L. Treating plants with 6 and 9 g/plant NPK + Actosol at 2.5 ml/L, gave tallest plants ,highest No. of branches and significantly increased the fresh and dry weights of plants, in both seasons. Reducing NPK from 12 to 9 or 6 g/plant increased significantly essential oil% ,and had a positive effect in both seasons. Actosol at 1.5 ml/L gave the highest oil % ,while at 2.5 ml/l gave the highest oil yield /plant. Twenty compounds were identified by GC-MS )βphellandrene, cyclohexanol, germacrene-D , α-pinene, geranyl acetate and 1,8-cineole(, were the dominant compounds, which increased with NPK (12 ,9 and 6 g/ plant) + Actosol 1.5 ml/L, in the first season, respectively. Decreasing NPK doses combined with high rate of Actosol increased the phenolic contents. The highest flavonoids content was recorded in plants treated with NPK 9g/plant + Actosol 1.5 ml/L(first season) and NPK 9 g/plant (second one). The antioxidant profile indicated that the crude extract in plants received 12g/plant NPK showed the highest IC50 in both seasons.

Essential oils and Flavonoids are widely recognized for their beneficial effects in possessing many biological activities, such as antioxidant, antimicrobial and cytotoxic properties, also using in food additives and in the cosmetic industry. The aim of this work is to produce nanoparticles of hesperidin and essential oil extracted from waste orange peels, and study its biological impact compared to native products (hesperidin and essential oil) as antioxidant, antimicrobial and cytotoxic. Obtained products (nano-formulation) are characterized by zeta potential, electron scanning microscopy, spectrophotometric method and color analysis. The final products (nano-formulation) were examined as antioxidant agent by two assays (DPPH and ABTS analysis). The antioxidant activity of nano hesperidin and essential oil was evaluated and compared with none formulated. Nanoparticles of hesperidin and essential oil have a great potential in DNA damage prevention compared to their respective controls which were examined by DNA damage assay induced by oxidative stress protection analysis. The in vitro cytotoxic activity of nano formulated hesperidin and essential oil, towards (three cancerous cell lines, including: breast (MCF-7), colorectal (HCT-116) and liver (HepG2), and two non-cancerous control cell lines (fibroblast BJ-1and MCF-12F) compared with native product (essential oil and hesperidin) were examined using MTT assay. The hesperidin and essential oil NPs showed a positive effect on the inhibition of the proliferation of all tested cancer cell line. The antimicrobial activity of hesperidin, essential oil and their nano formulation form was evaluated using well diffusion assay. The nano formulation form of hesperidin and essential oil showed to improve the antimicrobial activity. These findings showed that nano-hesperidin and nano - essential oils play an important role as antioxidant, antimicrobial and cytotoxic agent's effects. These effects might be used for clinical trials and can represent driving formulation for novel chemotherapeutic agents and in food industry. Further studies about the therapeutic effects of nano-hesperidin and essential oil extracted from Egyptian orange peel are requested

Dimethoate (technical and formulated) sublethal doses (1/20 of LD50) were ingested into male albino rats. The intoxicated rats were treated with cow and camel milk as an antitoxic diet to reduce the harmful of the pesticide (both forms). Energy compounds (ATP, ADP and AMP) as well as myokinase activity and also the respiratory system included cytochrome-c, Cytochrome-c-oxidase and succinate-cytochrome-c-reductase were studied in brain, liver and kidneys tissues of adult male albino rats during the experimental period of 3 months. LD50 of the technical and formulated dimethoate as well as the composition of cow and camel milks, were determined. ATP content of the three organs tissue was elevated, but the contents of ADP and AMP were reduced either by technical and formulated dimethoate effects relative to those of the normal healthy control. On the other hands, the effects of technical and formulated dimethoate on mitochondrial cytochrome-c contents and activity of Cytochrome-c-oxidase and succinate-cytochrome-c-reductase was studied. Cytochrome-c contents showed considerable decreases, but the activities of both enzymes of the mitochondrial respiratory system (cytochrome-c contents and Cytochrome-c-oxidase) were stimulated in liver, kidneys and brain tissues. In general, the formulated dimethoate ingestions were more toxic than the technical pesticide ingestions relative to those of normal healthy control. The treatment with Cow and camel milk as antioxidant agents observed antagonistic influence against the harmful of the present pesticide. The milk treatments attenuated the dimethoate toxicity and improved the organophosphorus pesticide disturbance in the present studied parameter. For energy system (ATP, ADP and AMP and also myokinase activity) as well as the respiratory system of cytochrome-c (cytochrome-c level, with cytochrome-c-oxidase and cytochrome-c-reductase activities) were about normalized nearly around of those values in brain, liver and kidneys tissues of the normal control. The desirable treatments of camel milk were more than those of cow milk treatments against the harmful of the technical and formulated dimethoate. In conclusion, the present investigation found that camel milk possesses a potential antitoxic effect and higher than those obtained by cow milk, these may be due to the presence of many beneficial agents. The therapeutic efficacy of camel milk has rather explained by lack of coagulation in an acidic condition of the animal stomach

Milk and milk products is implicated in many human health benefits. Several animals milk source are used for that porous such as cow, cheap, camel and goat. Goat milk has a unique composition compared to other animals. In this study, we investigate the antioxidant, antibacterial and anticancer potencies of casein and whey proteins of goat milk fractions crude methanol extract. As a result, whey protein extract exhibited high antioxidant activity than casein against stable radical DPPH and ABTS with IC50 value 0.12 and 0.237 µg/ml, respectively compared to casein fraction extract. The anticancer properties were investigated against two cancerous cell lines, including: breast (MCF-7) and liver (HepG2). Results of the MTT assay were in agreement of the antioxidants activity, when whey fraction methanol extract exhibited specific anticancer activities against MCF-7 cell line compared to casein and doxorubicin positive control. However, no cytotoxic activities of extract were observed against two non-cancerous control cell lines (BJ-1and MCF-12). Casein and whey proteins extract could prevent DNA damage induced by oxidative stress. The antimicrobial activity of goat milk methanol extract was tested against five bacterial strains including gram positive (Bacillus cereu EMCC 1080 and Staphylococcus ureuse ATCC 13565(, gram negative (Escherichia coli O157-H7 ATCC 51659, Salmonella typhi ATCC 15566 and Pseudomonas aeruginosa NRRL B-272. Among them, Bacillus cereu and Escherichia coli were extensively affected, when the inhibition zone was 4.3 and 5 cm, respectively. The fact that goat milk is enriched in features belonging to elements, vitamins and short peptide derivatives. In addition, goat milk has specific fat composition of the medium chain fatty acids led to increase the antioxidant and antibacterial and anticancer properties.

Nanoparticles are the basic essential element of nanotechnology and it exhibits characteristic features based on their properties such as size, morphology and other size dependent properties. Their applications on agriculture, food and medicine are widely used nowadays. Agro-waste materials cause a global environmental problem worldwide. Maximizing the benefits of such waste material is a very important issue. The present investigation aimed to use nano-formulation techniques by using polyethylene glycol 8000 to produce nano-lycopene extracted from tomato waste (pomace) as well as evaluation the antioxidant, antimicrobial and anticancer activity of produced lycopene-NPs. The results of antioxidant activity using ABTS and DPPH assays revealed that nano-formulation of Lycopene increases the scavenging activity compared with lycopene. Also, both lycopene and lycopene-NPs showed antibacterial activity against all tested bacteria and antifungal activity against tested fungal species. MIC for lycopene and lycopene-NPs was determined. DNA damage induced by oxidative stress protection analysis indicated that lycopene-NPs has a great potential in DNA damage prevention compared to their respective controls. The MTT assay exhibited cytotoxic activity against three cancerous cell lines, MCF-7, HCT-116 and HepG2. As well as lycopene-NPs biosafety was tested against normal cell lines (BJ-1 and MCF-12F) compared to lycopene.

Opuntia spp. is an economically important crop from the Cactaceae family and native to the tropical and subtropical regions of America. It is cultivated for various uses such as fresh fruit, pharmaceutical, cosmetic, or in the form of beverage. Opuntia spp. is well known for its anatomical and physiological characters to conserve water and tolerate extreme drought conditions. The production of Opuntia has been extended around the world and it has become an alternative crop in the areas with low-quality soil and water deficit. The ability to tolerate the extreme environments of Opuntia species makes them also valuable to study molecular mechanisms underlying abiotic stress tolerance. Opuntia is crassulacean acid metabolism (CAM) species with high water-use efficiencies (WUE) that makes it to be able to grow in areas with insufficient precipitation and less water availability to support traditional C3 or C4 bioenergy crops. Studies of photosynthesis have shown that these species use a particular photosynthetic pathway known as CAM for the fixation of atmospheric CO2 during the dry season. Indeed, in the CAM pathway as an adaptation mechanism in plants to water deficit, all or part of the atmospheric CO2 uptake occurs at the nighttime that remains stomata closer at daytime when the temperature is a higher and consequent reduction in the evapotranspiration rates. Atmospheric CO2 uptake ratio can affect the biomass production in plants. Despite, CO2 fixation in CAM plants is 15% more efficient than C3 plants, CAM species often grow slowly due to their extra enzymatic reactions for carbon fixation. In C3 plants, 3 ATP and 2 NADPH require for each CO2 molecular fixation, while in CAM plants for each CO2 fixation, 5.5–6.5 ATP and 2 NADPH are required. In CAM plants net carbon fixation efficiency is 10% less than C4 plants. However, under optimal growth conditions, Opuntia has the potential to produce higher biomass rivaling that of C3 and C4 crops. Moreover, growth character and CAM pathway in genera Opuntia, allow these species to operate at near-maximum productivity with relatively low water requirement. Cultivation of CAM species from the genera Opuntia can provide an alternative to product feedstocks and food in the arid and semiarid regions. For this purpose, here in this chapter, we will discuss (a) the crassulacean acid metabolism pathway; (b) the molecular mechanism of CAM; (c) physiological attributes of CAM during the drought tolerance period; (d) CAM improve Opuntia biomass production. Furthermore, screening Opuntia species that qualify with water use efficiency and high productivity will be interesting to be reviewed in this chapter to provide the alternative feedstock bioenergy crops that preserve and expand feedstock production in water-limited areas.

Natural plant-derived phenolic extract recently received much attention in the food industry to obtain bioactive compounds for food and pharmaceutical industries. These compounds are of considerable interest due to their medicinal and nutrition properties. In this line, cactus pear (Opuntia spp.) is considered for its potentially active nutrients and its multifunctional properties to produce health-promoting food supplements. These beneficial effects are related to its potential bioactive compounds like phenolic acids and flavonoids possessing antioxidant traits. As secondary metabolites, phenolic compounds can mitigate oxidative damage caused by cancer, cardiovascular diseases, and diabetes. The phenolic structure contains an aromatic ring with one or more hydroxyl groups that cause their therapeutic activity. Two classes of phenolic compounds are extensively investigated in the plants, including hydroxybenzoic acid and hydroxycinnamic acid. However, phenylpropanoid serves as a precursor for synthesizing the other phenolic compounds. Several phenolic compounds were found to display different health benefits, including antioxidant, anti-inflammatory, and anticancer activities. Phenolic acids and flavonoids from the genus Opuntia have been recognized as antioxidants. Phenolic acids such as vanillic, ferulic, p-coumaric, p-hydroxybenzoic, syringic, protocatechuic, caffeic, salicylic, gallic, and sinapic, as well as flavonoids such as rutin, isoquercitrin, kaempferol, and narcissi are found in plants from the genus Opuntia. The antioxidant properties of phenolic compounds in Opuntia spp. plants make them an essential product for preventing human health against degenerative diseases such as cancer, diabetes, hypercholesterolemia, arteriosclerosis, cardiovascular and gastric diseases. Nowadays, the food and agricultural processing include phenolic compounds as an essential part of the human diet. This chapter discusses the medicinal importance of phenolic compounds in Opuntia spp. as a natural antioxidant. The article highlights the extractions methods and manufacturing processing, including backing, cooking, and frying, in the food and beverage industry and their effects on these compounds’ stability and activity. This information would help identify Opuntia species rich in phenolics and their therapeutic properties. Besides, the chemical structure, properties, and health benefits of phenolic compounds of cactus pear fruit and their influences in agro-industrial wastes as natural sources of antioxidants with application in food industries have been reviewed.

39 p.-7 fig.-2 tab.-9 tab. supl., Microgreens are rich functional crops with valuable nutritional elements that have health benefits when used as food supplements. Growth characterization,nutritional composition profile of 21 varieties representing five species of the Brassica genus asmicrogreens were assessed under light-emitting diodes(LEDs) conditions. Microgreens were grown under four different LEDs ratios(%); red:blue 80:20 and 20:80 (R80:B20 and R20:B80), or red:green:blue 70:10:20 and 20:10:70 (R70:G10:B20 and R20:G10:B70). Results indicated that supplemental lighting with green LEDs (R70:G10:B20) enhanced vegetative growth and morphology, while blue LEDs (R20:B80) increased the mineral and vitamin contents. Interestingly, by linking the nutritional content with the growth yield to define the optimal LEDs setup, we found that the best lighting to promote the microgreen growth was the green LEDs combination (R70:G10:B20). Remarkably, under the green LEDs combination (R70:G10:B20) conditions,the microgreens of Kohlrabi purple, Cabbage red, Broccoli, Kale Tucsan, Komatsuna red, Tatsoi and Cabbage green, which can benefit human health in conditions with limited food, had the highest growth and nutritional content., This research work is a part of a project received seed funding from the Dubai Future Foundation through the Guaana.com open research platform(grant no. MBR026). Dr. Mortaza is supported from ERDF project “Plants as a tool from sustainable global development” No. CZ.02.1.01/0.0/0.0/16_019/0000827.

Royal jelly (RJ) is a highly valued natural product which has long been used as a functional food in various parts of the world. The aim of this study was to evaluate the effects of RJ supplementation (0.5%, 1%, and 1.5%, w/w) on physicochemical properties (i.e., viscosity, chemical composition, water holding capacity, antioxidant activity), organoleptic characteristics, culture viability, and biological activities (i.e., anticancer and antibacterial activities) of fermented milk. Results showed RJ supplementation could reduce the fermentation time, increase the viscosity and water holding capacity, and also enhance the antioxidant acitivity of fermented milk. Compared to the fermented milk without RJ addition, fermented milk with 1% RJ had significantly more probiotics Lactobacillus helveticus Lh-B02, approximately 9.73 log CFU/g during 21 days of cold storage. Additionally, RJ supplementation could greatly boost the bioactivities of fermented milk. Fermented milk with 1.5% RJ had the highest anticancer and antibacterial properties, whereas the one with 1% RJ had the best sensory attribute score. Overall, RJ has a great potential to be a viable dietary additive for the development of innovative dairy products with multifacet nutritional and bioactive properties.

The anticancer activity of natural compounds has recently attracted multidisciplinary research. In this study, the complexation of milk proteins (MP) with Isabgol husk mucilage (IHM) and Ziziphus spina-christi mucilage (NabM) was investigated. In this context, the physicochemical properties of milk protein mucilage complexes (MPMC) including pH, Carr’s index, water solubility, and water absorption indices were measured, and the flow behavior was studied. In addition, the amino acid profile, protein digestibility, and phenolic and flavonoids content of MPMC were explored, and the microstructure of the complexes was visualized using transmission electron microscopy. The antioxidant and anticancer potencies of MPMC against two cancerous cell lines, human liver cancer HEPG-2 and breast cancer MCF-7, in comparison with two normal cell lines, namely, Bj-1 and MCF-12F, were tested using neutral red uptake assay. The results revealed that MPMC had scavenging activity against DPPH, ABTS, and HS radicals. Moreover, MPMC has the potential to prevent DNA damage induced by oxidative stress in Type-Fenton’s reaction. The results of the neutral red assay showed significant growth inhibition of both HEPG-2, MCF-7, whereas no significant cytotoxic effect was detected against Bj-1 and MCF-12F. RT-qPCR results indicated MPMC stimulated apoptosis as revealed by the upregulation of the pro-apoptosis gene markers Casepase-3, p53, Bax. Meanwhile, the anti-apoptosis Bcl-2 gene was downregulated. However, no significant difference was observed in normal cell lines treated with MPMC. In conclusion, MPMC can be considered as a promising anticancer entity that can be used in the development of novel cancer therapeutics with comparable activity and minimal side effects compared to conventional cancer chemotherapies.

Microgreens are rich functional crops with valuable nutritional elements that have health benefits when used as food supplants. Growth characterization, nutritional composition profile of 21 varieties representing 5 species of the Brassica genus as microgreens were assessed under light-emitting diodes (LEDs) conditions. Microgreens were grown under four different LEDs ratios (%) (R80:B20, R20:B80, R70:G10:B20, and R20:G10:B70). Results indicated that supplemental lighting with green LEDs (R70:G10:B20) enhanced vegetative growth and morphology, while blue LEDs (R20:B80) increased the mineral composition and vitamins content. Interestingly, combining the nutritional content with the growth yield to define the optimal LEDs setup, we found that the best lighting to promote the microgreen growth was supplying the green LEDs combination (R70:G10:B20). Remarkably, under this proper conditions, Kohlrabi purple, Cabbage red, Broccoli, Kale Tucsan, Komatsuna red, Tatsoi, and Cabbage green had the highest growth and nutritional content profile as microgreens which being a health-promoting in a diet support strategy required for the human health under certain isolated of limited food conditions.

Background: Rosin (Colophony) is a natural resin derived from species of the pine family Pinaceae. It has wide industrial applications including printing inks, photocopying paper, adhesives and varnishes, soap and soda. Rosin and its derivatives are employed as ingredients in various pharmaceutical products such as ointments and plasters. Rosin-based products contain allergens that may exert some occupational health problems such as asthma and contact dermatitis. Objective: Our knowledge of the pharmaceutical and medicinal properties of rosin is limited. The current study aims at investigating the cytotoxic potential of Rosin-Derived Crude Methanolic Extract (RD-CME) and elucidation of its mode-of-action against breast cancer cells (MCF-7 and MDA-MB231). Methods: Crude methanol extract was prepared from rosin. Its phenolic contents were analyzed by Reversed- Phase High-Performance Liquid Chromatography (RP-HPLC). Antioxidant activity was evaluated by DPPH radical-scavenging assay. Antiproliferation activity against MCF-7 and MDA-MB231 cancerous cells was investigated by MTT assay; its potency compared with doxorubicin as positive control and specificity were assessed compared to two non-cancerous cell lines (BJ-1 and MCF-12F). Selected apoptosis protein markers were assayed by western blotting. Cell cycle analysis was performed by Annexin V-FITC/PI FACS assay. Results: RD-CME exhibited significant and selective cytotoxicity against the two tested breast cancer cells (MCF-7 and MDA-MB231) compared to normal cells as revealed by MTT assay. ELISA and western blotting indicated that the observed antiproliferative activity of RD-CME is mediated via the engagement of an intrinsic apoptosis signaling pathway, as judged by enhanced expression of key pro-apoptotic protein markers (p53, Bax and Casp 3) relative to vehicle solvent-treated MCF-7 control cells. Conclusion: To our knowledge, this is the first report to investigate the medicinal anticancer and antioxidant potential of crude methanolic extract derived from colophony rosin. We provided evidence that RD-CME exhibits strong antioxidant and anticancer effects. The observed cytotoxic activity against MCF-7 is proposed to take place via G2/M cell cycle arrest and apoptosis. Colophony resin has a great potential to join the arsenal of plantderived natural anticancer drugs. Further thorough investigation of the potential cytotoxicity of RD-CME against various cancerous cell lines is required to assess the spectrum and potency of its novel activity.

Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the MTT assay revealed that chloroform (CHCl3) and ethyl acetate (EtOAc)-soluble fractions exhibited specific anticancer activities as marginal toxicities were observed against two non-cancerous control cell lines (BJ-1 and MCF-12). Ultra-high-resolution mass spectrometry Q-Exactive&trade, HF Hybrid Quadrupole-Orbitrap&trade, coupled with liquid chromatography (UHPLC) indicated that both extracts are enriched in features belonging to major phenolic and purine derivatives. Fluorescence-activated cell sorter analysis (FACS), employing annexin V-FITC/PI double staining indicated that the observed cytotoxic potency was mediated via apoptosis. FACS analysis, monitoring the increase in fluorescence signal, associated with oxidation of DCFH to DCF, indicated that the mechanism of apoptosis is independent of reactive oxygen species (ROS). Results of immunoblotting and RT-qPCR assays showed that treatment with organic fractions under investigation resulted in significant up-regulation of pro-apoptotic protein and mRNA markers for Caspase-3, p53 and Bax, whereas it resulted in a significant reduction in amounts of both protein and mRNA of the anti-apoptotic marker Bcl-2. FACS analysis also indicated that pre-treatment and co-treatment of human amniotic epithelial (WISH) cells exposed to the ROS H2O2 with EtOAc fraction provide a cytoprotective and antioxidant capacity against generated oxidative stress. In conclusion, our findings highlight the importance of natural phenolic and flavonoid compounds with unparalleled and unique antioxidant and anticancer properties.

The present work aims to design and synthesize novel series of spiro pyrazole-3,3&rsquo, oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7, colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC50 values obtained were 5.7&ndash, 21.3 and 5.8&ndash, 37.4 &micro, g/mL against HCT-116 and MCF-7, respectively, which is 3.8 and 6.5-fold (based on the least IC50 values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h the highest cytotoxicity with IC50 value of 19.2&micro, g/mL relative to doxorubicin (IC50 = 21.6&micro, g/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells.

Colon cancer represents a huge health problem to the patients due to the high incidence and mortality rates. This study was focused on investigating the anticancer effects of methanolic extracts of the aerial parts of Agave americana and Agave micrantha. Then, the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was done to study the cytotoxic activities of these extracts in vitro on cell line HCT 116 that is of a human colon cancer origin. In addition, cytotoxicity was studied in the normal human epithelial cell line RPE1. Additionally, the morphological changes of HCT 116 cells upon exposure to these plant extracts were studied using the inverted microscope. Results showed a significant antiproliferative and anticancer activities of Agave Americana extract at concentrations 12.5, 25 and 50 and 100 µg/ml with IC50 of 73.7 µg/ml. Exposure of HCT 116 cells to this plant extract resulted in more altered cell shapes from polygonal to circular with cell shrinkage. Conversely, the extract of Agave micrantha did not exert any significant cytotoxic effects or morphological changes on HCT 116 cells. In addition, both extracts did not show cytotoxicity in normal RPE1 cells. Extract of Agave Americana is recommended for further anticancer investigations that might result in isolation and development of effective anticancer drug.

SummaryDE-ETIOLATED 1 (DET1) is an evolutionarily conserved component of the ubiquitination machinery that mediates the destabilization of key regulators of cell differentiation and proliferation in multicellular organisms. In this study, we provide evidence from Arabidopsis that DET1 is essential for the regulation of histone H2B monoubiquitination (H2Bub) over most genes by controlling the stability of a plant deubiquitination module (DUBm). In contrast with yeast and metazoan DUB modules that are associated with the large SAGA complex, the Arabidopsis DUBm only comprises three proteins (hereafter named SGF11, ENY2 and UBP22) and appears to act independently as a major H2Bub deubiquitinase activity. Our study further unveils that DET1-DDB1-Associated-1 (DDA1) protein interacts with SGF11in vivo, linking the DET1 complex to light-dependent ubiquitin-mediated proteolytic degradation of the DUBm. Collectively, these findings uncover a signaling path controlling DUBm availability, potentially adjusting H2Bub turnover capacity to the cell transcriptional status.

The aim of this study was to evaluate the potential anticancer properties and modulatory effect of selected Aloe vera (A. vera) active principles on antioxidant enzyme activities. Thus, three anthraquinones (Namely: aloesin, aloeemodin and barbaloin) were extracted from A. vera leaves by supercritical fluid extraction and subsequently purified by high performance liquid chromatography. Additionally, the N-terminal octapeptide derived from verectin, a biologically active 14 kDa glycoprotein present in A. vera, was also tested. In vivo, active principles exhibited significant prolongation of the life span of tumor-transplanted animals in the following order: barbaloin > octapeptide > aloesin > aloe-emodin. A. vera active principles exhibited significant inhibition on Ehrlich ascite carcinoma cell (EACC) number, when compared to positive control group, in the following order: barbaloin > aloe-emodin > octapeptide > aloesin. Moreover, in trypan blue cell viability assay, active principles showed a significant concentration-dependent cytotoxicity against acute myeloid leukemia (AML) and acute lymphocytes leukemia (ALL) cancerous cells. Furthermore, in MTT cell viability test, aloeemodin was found to be active against two human colon cancer cell lines (i.e. DLD-1 and HT2), with IC50 values of 8.94 and 10.78 μM, respectively. Treatments of human AML leukemic cells with active principles (100 μg ml-1) resulted in varying intensities of internucleosomal DNA fragmentation, hallmark of cells undergoing apoptosis, in the following order: aloe-emodin > aloesin > barbaloin > octapeptide. Intererstingly, treatment of EACC tumors with active principles resulted in a significant elevation activity of key antioxidant enzymes (SOD, GST, tGPx, and LDH). Our data suggest that the tested A. vera compounds may exert their chemo-preventive effect through modulating antioxidant and detoxification enzyme activity levels, as they are one of the indicators of tumorigenesis. These findings are discussed in the light of the potential of A. vera plant extracts for developing efficient, specific and non-toxic anticancer drugs that are affordable for developing countries.