Natural Products as Cytotoxic Agents in Chemotherapy against Cancer

Nature continues to produce a great wealth of natural molecules endowed with cytotoxic activity toward a large panel of tumor cells. Some of these molecules are used in chemotherapy, and others have shown great anti-tumor and anti-metastatic potential in preclinical trials. This review discusses some examples of these molecules that have been studied in our laboratory and others. We report a differential cytotoxic activity of some monoterpenes (carvacrol, tymol, carveol, carvone, and isopulegol) against a panel of tumor cell lines. The carvacrol was the most cytotoxic molecule both in vitro and in vivo as demonstrated by preclinical studies using the DBA2/P815 mice model. On the other hand, polyphenols were also studied with respect to their cytotoxic effects. Interestingly, these compounds showed a prominent cytotoxic activity toward a panel of cancer cells with differential molecular mechanisms. In addition, we report a very strong antitumor efficacy of artemisinin, a sesquiterpen lactone from Artemisia annua, together with an antimetastatic potential as demonstrated by preclinical experiments. Furthermore, some of the molecular mechanisms involved in these effects are described

Chemical Composition and Cytotoxic and Antibacterial Activities of the Essential Oil of Aloysia citriodora

The aim of this work is to investigate the in vitro cytotoxic and antibacterial effects of the essential oils of Aloysia citriodora Palau, harvested in different regions of Morocco. The chemical profile was established using gas chromatography-mass spectrometry analysis. The cytotoxic activity against P815, MCF7, and VERO cell lines as well as the normal human peripheral blood mononuclear cells (PBMCs) was evaluated using the MTT assay. Standard, ATCC, strains of bacteria (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) were cultivated in Muller Hinton media. Then, agar disc diffusion, minimum inhibitory concentrations (MICs), and minimal bactericidal concentrations (MBCs) were determined using microdilution method. The essential oils obtained were predominantly composed of β-spathulenol (15.61%), Ar-curcumene (14.15%), trans-caryophyllene oxide (14.14%), and neral (10.02%). The results of the assays showed that the cytotoxic effect of the essential oil of A. citriodora was high on P815 and moderate on MCF7 and on VERO cell lines. However, no cytotoxic effect was observed on PBMCs. On the other hand, essential oils showed a significant antimicrobial activity against both Gram-negative and Gram-positive bacteria. MICs ranged between 2.84 and 8.37 mg/ml. Essential oil of A. citriodora leaves possesses significant antibacterial effect and cytotoxic activity against tumor cell lines

Treatment of table olive processing wastewaters using novel photomodified ultrafiltration membranes as first step for recovering phenolic compounds

Table olive processing wastewaters (TOPW) have high salt concentration and total phenolic content (TPC) causing many environmental problems. To reduce them, ultrafiltration (UF) was applied for treating TOPW. However, NaCl, which is the main responsible of salinity in TOPW, and phenols are small molecules that cannot be separated by conventional UF membranes. They have serious problems caused by fouling, which can be overcome using membrane modification techniques. For these reasons, photomodification may be an effective technique to obtain a stream rich in TPC due to the changes in membrane surface properties. UV-modification in the presence of two hydrophilic compounds (polyethylene glycol and aluminium oxide) was performed to achieve membranes with high reductions of organic matter and to keep the TPC as high as possible. Commercial polyethersulfone (PES) membranes of 30 kDa were used. Surface modification was evaluated using FTIR-ATR spectroscopy and membrane performance was studied by calculating the rejection ratios of colour, chemical oxygen demand (COD) and TPC. Results demonstrated that UF is a useful pre-treatment to reduce organic matter from TOPW, obtaining a permeate rich in TPC. PES/Al2O3 membranes displayed superior antifouling properties and rejection values, keeping high the TPC (>95%). Therefore, UF using modified membranes is an appropriate and sustainable technique for treating TOPW.The authors thank the financial support of CDTI (Centre for Industrial Technological Development) depending on the Spanish Ministry of Science and Innovation. The authors also thank the Center for Biomaterials and Tissue Engineering (Universitat Politecnica de Valencia) for FTIR-ATR and contact angle measurements.García Ivars, J.; Iborra Clar, MI.; Alcaina Miranda, MI.; Mendoza Roca, JA.; Pastor Alcañiz, L. (2015). Treatment of table olive processing wastewaters using novel photomodified ultrafiltration membranes as first step for recovering phenolic compounds. Journal of Hazardous Materials. 290:51-59. doi:10.1016/j.jhazmat.2015.02.062S515929

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

Fluorescence spectroscopy for wastewater monitoring: A review

© 2016. Wastewater quality is usually assessed using physical, chemical and microbiological tests, which are not suitable for online monitoring, provide unreliable results, or use hazardous chemicals. Hence, there is an urgent need to find a rapid and effective method for the evaluation of water quality in natural and engineered systems and for providing an early warning of pollution events. Fluorescence spectroscopy has been shown to be a valuable technique to characterize and monitor wastewater in surface waters for tracking sources of pollution, and in treatment works for process control and optimization. This paper reviews the current progress in applying fluorescence to assess wastewater quality. Studies have shown that, in general, wastewater presents higher fluorescence intensity compared to natural waters for the components associated with peak T (living and dead cellular material and their exudates) and peak C (microbially reprocessed organic matter). Furthermore, peak T fluorescence is significantly reduced after the biological treatment process and peak C is almost completely removed after the chlorination and reverse osmosis stages. Thus, simple fluorometers with appropriate wavelength selectivity, particularly for peaks T and C could be used for online monitoring in wastewater treatment works. This review also shows that care should be taken in any attempt to identify wastewater pollution sources due to potential overlapping fluorophores. Correlations between fluorescence intensity and water quality parameters such as biochemical oxygen demand (BOD) and total organic carbon (TOC) have been developed and dilution of samples, typically up to ×10, has been shown to be useful to limit inner filter effect. It has been concluded that the following research gaps need to be filled: lack of studies on the on-line application of fluorescence spectroscopy in wastewater treatment works and lack of data processing tools suitable for rapid correction and extraction of data contained in fluorescence excitation-emission matrices (EEMs) for real-time studies

Approches de développement territorial par la mise en tourisme montagnard au Maroc : cas de la province d’Azilal

This thesis is a contribution to a general framework of territory, built essentially around three main levels. First of all, the mountain as a territory marked by its multiple difficulties, but also by considerable assets and singularities of an economic and tourist nature in particular. Second, the success of international experiences in the field of mountain tourism as a major interest for the territorial economy. Finally, the importance and the multitude of interactions between mountains and tourism as driving dynamics for the sustainable economic, cultural and social development of local populations. The interlinked nature of mountain tourism means that this thesis is essentially concerned with two social science disciplines: economics and geography. Within this framework, we will specifically study the perspectives of territorial development on the basis of a territorial construction of economic and social dynamics, in order to analyse from a multidimensional angle the tourism potential of the four municipalities chosen as a study laboratory. On the other hand, the socio-economic, human and environmental effects and impacts will be assessed and measured. The selected communes are a real example of the replication of the territorial resources promotion process to innovate and develop new uses and new forms of tourism within the framework of a Territorialised Touristic System in the Azilal province.La présente thèse se veut une contribution dans un cadre général du territoire, bâti essentiellement autour de trois niveaux principaux. D’abord, la montagne en tant que territoire marqué par ses multiples difficultés, mais également par des atouts et des singularités considérables d’ordre économique et touristique en particulier. Ensuite, le succès des expériences internationales en matière de mise en tourisme de la montagne comme intérêt majeur pour l’économie territoriale. Enfin, l’importance et la multitude des interactions entre la montagne et le tourisme en tant que dynamiques motrices du développement économique, culturel et social durable des populations locales. La nature interdépendante du tourisme de montagne fait que la présente thèse s’inscrit principalement dans deux disciplines des sciences sociales : l’économie et la géographie. Dans ce cadre, nous étudierons spécifiquement les perspectives de développement territorial basé sur une construction territoriale de dynamiques économique et sociale, pour analyser sous un angle multidimensionnel le potentiel touristique des quatre communes choisies en tant que laboratoire d’étude. De l’autre côté, il s’agit d’évaluer et de mesurer les effets et les retombées socio-économiques, humains et environnementaux. Les communes choisies sont un exemple réel de la réitération des processus de valorisation des ressources territoriales pour innover et valoriser de nouveaux usages et de nouvelles formes de tourisme dans le cadre d’un Système Touristique Territorialisé dans la province d’Azilal

Territorial development approaches through mountain tourism in Morocco : the case of the province of Azilal

La présente thèse se veut une contribution dans un cadre général du territoire, bâti essentiellement autour de trois niveaux principaux. D’abord, la montagne en tant que territoire marqué par ses multiples difficultés, mais également par des atouts et des singularités considérables d’ordre économique et touristique en particulier. Ensuite, le succès des expériences internationales en matière de mise en tourisme de la montagne comme intérêt majeur pour l’économie territoriale. Enfin, l’importance et la multitude des interactions entre la montagne et le tourisme en tant que dynamiques motrices du développement économique, culturel et social durable des populations locales. La nature interdépendante du tourisme de montagne fait que la présente thèse s’inscrit principalement dans deux disciplines des sciences sociales : l’économie et la géographie. Dans ce cadre, nous étudierons spécifiquement les perspectives de développement territorial basé sur une construction territoriale de dynamiques économique et sociale, pour analyser sous un angle multidimensionnel le potentiel touristique des quatre communes choisies en tant que laboratoire d’étude. De l’autre côté, il s’agit d’évaluer et de mesurer les effets et les retombées socio-économiques, humains et environnementaux. Les communes choisies sont un exemple réel de la réitération des processus de valorisation des ressources territoriales pour innover et valoriser de nouveaux usages et de nouvelles formes de tourisme dans le cadre d’un Système Touristique Territorialisé dans la province d’Azilal.This thesis is a contribution to a general framework of territory, built essentially around three main levels. First of all, the mountain as a territory marked by its multiple difficulties, but also by considerable assets and singularities of an economic and tourist nature in particular. Second, the success of international experiences in the field of mountain tourism as a major interest for the territorial economy. Finally, the importance and the multitude of interactions between mountains and tourism as driving dynamics for the sustainable economic, cultural and social development of local populations. The interlinked nature of mountain tourism means that this thesis is essentially concerned with two social science disciplines: economics and geography. Within this framework, we will specifically study the perspectives of territorial development on the basis of a territorial construction of economic and social dynamics, in order to analyse from a multidimensional angle the tourism potential of the four municipalities chosen as a study laboratory. On the other hand, the socio-economic, human and environmental effects and impacts will be assessed and measured. The selected communes are a real example of the replication of the territorial resources promotion process to innovate and develop new uses and new forms of tourism within the framework of a Territorialised Touristic System in the Azilal province

Approches de développement territorial par la mise en tourisme montagnard au Maroc : cas de la province d’Azilal

This thesis is a contribution to a general framework of territory, built essentially around three main levels. First of all, the mountain as a territory marked by its multiple difficulties, but also by considerable assets and singularities of an economic and tourist nature in particular. Second, the success of international experiences in the field of mountain tourism as a major interest for the territorial economy. Finally, the importance and the multitude of interactions between mountains and tourism as driving dynamics for the sustainable economic, cultural and social development of local populations. The interlinked nature of mountain tourism means that this thesis is essentially concerned with two social science disciplines: economics and geography. Within this framework, we will specifically study the perspectives of territorial development on the basis of a territorial construction of economic and social dynamics, in order to analyse from a multidimensional angle the tourism potential of the four municipalities chosen as a study laboratory. On the other hand, the socio-economic, human and environmental effects and impacts will be assessed and measured. The selected communes are a real example of the replication of the territorial resources promotion process to innovate and develop new uses and new forms of tourism within the framework of a Territorialised Touristic System in the Azilal province.La présente thèse se veut une contribution dans un cadre général du territoire, bâti essentiellement autour de trois niveaux principaux. D’abord, la montagne en tant que territoire marqué par ses multiples difficultés, mais également par des atouts et des singularités considérables d’ordre économique et touristique en particulier. Ensuite, le succès des expériences internationales en matière de mise en tourisme de la montagne comme intérêt majeur pour l’économie territoriale. Enfin, l’importance et la multitude des interactions entre la montagne et le tourisme en tant que dynamiques motrices du développement économique, culturel et social durable des populations locales. La nature interdépendante du tourisme de montagne fait que la présente thèse s’inscrit principalement dans deux disciplines des sciences sociales : l’économie et la géographie. Dans ce cadre, nous étudierons spécifiquement les perspectives de développement territorial basé sur une construction territoriale de dynamiques économique et sociale, pour analyser sous un angle multidimensionnel le potentiel touristique des quatre communes choisies en tant que laboratoire d’étude. De l’autre côté, il s’agit d’évaluer et de mesurer les effets et les retombées socio-économiques, humains et environnementaux. Les communes choisies sont un exemple réel de la réitération des processus de valorisation des ressources territoriales pour innover et valoriser de nouveaux usages et de nouvelles formes de tourisme dans le cadre d’un Système Touristique Territorialisé dans la province d’Azilal

Olive Mill Waste Extracts: Polyphenols Content, Antioxidant, and Antimicrobial Activities

Natural polyphenols extracts have been usually associated with great bioactive properties. In this work, we investigated in vitro antioxidant and antimicrobial potential of the phenolic olive mill wastewater extracts (OWWE) and the olive cake extracts (OCE). Using the Folin Ciocalteux method, OWWE contained higher total phenol content compared to OCE (8.90±0.728 g/L versus 0.95±0.017 mg/g). The phenolic compounds identification was carried out with a performance liquid chromatograph coupled to tandem mass spectrometry equipment (HPLC-ESI-MS). With this method, a list of polyphenols from OWWE and OCE was obtained. The antioxidant activity was measured in aqueous (DPPH) and emulsion (BCBT) systems. Using the DPPH assay, the results show that OWWE was more active than OCE and interestingly the extracts originating from mountainous areas were more active than those produced from plain areas (EC50=12.1±5.6 μg/mL; EC50=157.7±34.9 μg/mL, resp.). However, when the antioxidant activity was reversed in the BCBT, OCE produced from plain area was more potent than mountainous OCE. Testing by the gel diffusion assay, all the tested extracts have showed significant spectrum antibacterial activity against Staphylococcus aureus, whereas the biophenols extracts showed more limited activity against Escherichia coli and Streptococcus faecalis