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A Methanol Extract of Scabiosa atropurpurea Enhances Doxorubicin Cytotoxicity against Resistant Colorectal Cancer Cells In Vitro
Vitro.Imene Ben Toumia , Mansour Sobeh, Marco Ponassi, Barbara Banelli, Anas Dameriha, Michael Wink, Leila Chekir Ghedira and Camillo Rosano

Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of Scabiosa atropurpurea and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. S. atropurpurea extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 c

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Chemical Composition and Cytotoxic Activity of the Fractionated Trunk Bark Essential Oil from Tetraclinis articulata (Vahl) Mast. Growing in Tunisia
Tunisia.Salma Jlizi, Aida Lahmar, Afifa Zardi Bergaoui, Roberta Ascrizzi, Guido Flamini, Abdelhalim Harrath, Leila Chekir-Ghedira, Hichem Ben Jannet.

The aim of the present research was to determine the chemical composition and the cytotoxic effects of Tetraclinis articulata trunk bark essential oil (HEE) obtained by steam distillation and five fractions obtained by normal phase silica chromatographic separation. Chemical analysis allowed the identification of 54 known compounds. Relatively high amounts of oxygenated sesquiterpenes (44.4–70.2%) were detected, mainly consisting of caryophyllene oxide (13.1–26.6%), carotol (9.2–21.2%),14-hydroxy-9-epi-(E)-caryophyllene (3.2–15.5%) and humulene epoxide II (2.6–7.2%). The cytotoxic activity against human mammary carcinoma cell lines (MDA-MB-231) and colorectal carcinoma cell lines (SW620) of the essential oil and its fractions were assessed. All the samples displayed moderate to weak activity compared to 5-fluorouracil. The colorectal carcinoma cell line was relatively more sensitive to the essential oil and its fractions compared to the breast cancer cell line, showing IC50 values from

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Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein
Lahmar Aida , Mathey Aline , Aires Verginie., Elgueder Dorra,Anne Vejux., Khlifi Rihab,Fairouz Sioud ,Leila Chekir Ghedira and Dominique Delmas,

The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combin

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Luteolin Induced Apoptosis and Blockage of P-Glycoprotein in Human Sarcoma Cell Lines
Dorra El Gueder , Aida Lahmar, Zaineb Dhaouefli, Imen Ben Toumia , Fairouz Sioud, Aicha Sassi,Jose Luis , Leila Chekir-Ghedira,

Resistance to chemotherapy is the main problem in the treatment of cancer. In many cases, this resistance is due to the over-expression of the P-glycoprotein (pg-p) that pumped out therapeutic drugs. Luteolin, a natural flavonoïd, is abundant in our daily diet and has many pharmacological properties. A large body of evidence shows that luteolin is a potent anti-cancer agent. In the present study, cell growth was assessed by MTT assay. Reactive oxygen species generation was measured with DCFH-DA staining; mitochondrial membrane potential was tested with rhodamine-123 using fluorometer, cell apoptosis was detected with flow cytometry and acridine orange staining, DNA damage was visualized by comet test and salting out method. Finally, drugs transporter activity of was measured by flow cytometry. Results indicated that luteolin could significantly inhibit growth of human sarcoma cells. In addition, analysis of various parameters indicated that luteolin induced apoptosis by generation of

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Essential Oil and Hydrophilic Antibiotic Co-Encapsulation in Multiple Lipid Nanoparticles : Proof of concept and In Vitro Activity against Pseudomonas aeruginosa
Rayhane Ben Khalifa ;Frédéric Bustos Gaspar ,Cristina Pereira , Leila Chekir Ghedira and Soraya Rodriguez-Rojo Antibiotics,

In the worldwide context of an impending emergence of multidrug-resistant bacteria, this research combined the advantages of multiple lipid nanoparticles (MLNs) and the promising therapeutic use of essential oils (EOs) as a strategy to fight the antibiotic resistance of three Pseudomonas aeruginosa strains with different cefepime (FEP) resistance profiles. MLNs were prepared by ultrasonication using glyceryl trioleate (GTO) and glyceryl tristearate (GTS) as a liquid and a solid lipid, respectively. Rosemary EO (REO) was selected as the model EO. REO/FEP-loaded MLNs were characterized by their small size (~110 nm), important encapsulation efficiency, and high physical stability over time (60 days). An assessment of the antimicrobial activity was performed using antimicrobial susceptibility testing assays against selected P. aeruginosa strains. The assays showed a considerable increase in the antibacterial property of REO-loaded MLNs compared with the effect of crude EO, especially again

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Chemical Composition and Cytotoxic Activity of Eucalyptus torquata Luehm. and Eucalyptus salmonophloia F. Muell. Trunk Bark Essential Oils against Human SW620 and MDA-MB-231 Cancer Cell Lines
Ghofrane Lahmadi, Aida Lahmar, Mansour Znati, Mohamed Tahar Elaieb, Mohamed Larbi Khouja, Roberta Ascrizzi, Guido Flamini, Abdel Halim Harrath, Leila Chekir-Ghedira, Hichem Ben Jannet

In recent years, there has been a growing interest in the screening of natural active ingredients from Eucalyptus essential oils because of their evident importance in practical utility and their undeniable therapeutic properties. Based on this, the aim of the present study was to investigate the chemical profile of the essential oils of the trunk bark of Eucalyptus torquata Luehm. (ETEO), and E. salmonophloia F. Muell. (ESEO), growing in Tunisia. The in vitro cytotoxic properties of the extracted EOs were also evaluated against two human cancer cell lines: breast carcinoma cell lines MDA-MB-231 and colorectal cancer cell lines SW620. The analysis by gas chromatography coupled with mass spectrometry (GC/MS) led to the identification of 32 compounds from the ETEO, with the dominant constituents being the monoterpenes trans-myrtanol (73.4 %) and myrtenol (4.7 %), and the apocarotene (E)-β-ionone (3.9 %). In the case of ESEO, 29 compounds were identified with trans-myrtanol (25.0 %), deca

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