Hala Kamel Khalife

Associate professor
Life & Earth Sciences department - Section I - Hadath
Speciality: Biology
Specific Speciality: Ageing and Nutrition

Teaching 5 Taught Courses
(2014-2015) APLB 580 - Master thesis

M2 Applied Plant Biotechnology

(2014-2015) Biol 240 - Cell Biology Lab (Histology, Embryology, Reproduction, and genetics)

BS Earth and life sciences

(2014-2015) Biol 281 - Cell Biology Lab (Histology, Embryology, and Reproduction)

BS Biochemistry

(2014-2015) Biol 330 - Nutrition

BS Earth and life sciences

(2014-2015) Biol 350 - Nutrition Lab

BS Earth and life sciences

Conferences 25 participations
Arab Health Exibition and Congress

2015-01-26 to 2015-01-29

Steam Cell Educational and Medical Symposium

2014-05-29 to 2014-05-30

Abstract of the 60 National Congress of the Italian Physiological Society, Siena, Italy.

Poster session
2009-09-23 to 2009-09-25

Italian-Polish-Japanese International Forum on Oxidative Stress and Aging

2008-09-12 to 2008-09-13

Statistics for the Design and Analysis of Reaserch Studies

2006-10-18 to 2006-10-21

L'attivita' Sportiva Nell'Approccio Ad Un EquilibrioPsico-Fisico

2006-10-06 to 2006-10-06

theoric-Practice course in Accelerated Solvent Extraction: Applicazioni Nelle Bioscenze

Summer School
2006-06-13 to 2006-06-13

Ruolo Di Antiossidanti Naturali Nella Prevenzione Di Ptologie

2006-05-27 to 2006-05-28

practice-Teoric cousre in REAL-TIME PCR

Summer School
2006-05-03 to 2006-05-04

Prespective of Metabonomics and Proteomics Investigations in Clinical Science

2006-03-29 to 2006-03-30

Approcio Interdisciplinare Nel Trattamento Dell'obesita'

2005-12-16 to 2005-12-16

Metallotioneina' Un Biomarker di Inquinamento Da metalli

2005-11-21 to 2005-11-21


Poster session
2005-06-15 to 2005-06-17

La Protromica in Diagnostica

2005-05-04 to 2005-05-04

Comunnicare Efficaciamente in Situazioni di Stress ad Ansia da Prestazioni

2005-04-27 to 2005-07-27

Carateristiche Nutrizionali Del Latte: Aspetti Comparativi

2005-03-06 to 2005-03-06

Ossidazione Della Diidrofolato Reduttasi: Possibili Implicazioni Nei Processi Neurodegerativi

2005-03-03 to 2005-03-03

Situazione Sanitaria in Paesi Emergenti Dell'Africa

2005-01-13 to 2005-01-13

Spectral Properties of a Photosensitizer MC450 and Their Applications

2004-12-07 to 2004-12-07

Crosstalk Between photosynthesis and and Enzyme Photoregulation in Plant Cells

2004-10-21 to 2004-10-21

Aggiornamenti in Chimica Clinica

2004-06-28 to 2004-06-28

Le Micotossine e la Sicurezza Alimentare

2004-06-09 to 2004-06-09

Encefalopatie Spongiformi

2004-06-08 to 2004-06-08

Doping e Antidoping

2004-02-18 to 2004-02-18

Radicali Liberi ed Antiossidanti

2004-02-12 to 2004-02-13

Publications 6 publications
Fornari E.2*, Nadembega P. 3, Quassinti L.1, Bramucci M.1, Khalife K.H. 5, Poli F.3, Gali Muhtasib H.4 and Lupidi G.1 Cytotoxic activity of the leaf extract of Gardenia sokotensis (Hutch) against human colon cancer cells enzofornari@hotmail.co.uk 2014

Plants represent a reservoir of diverse templates that are being tapped as a source of novel anticancer agents. Gardenia sokotensis (family Rubiaceae) has been reported to have antifebrile activities and is used especially for the treatment of malaria in the Burkina Faso region. The effects of Gardenia sokotensis on cancer cells are still unknown. Here we evaluated the anti-proliferative activity of the ethanolic extract of Gardenia sokotensis leaves on different human cancer cell lines to explore its potential anti-carcinogenic effects. The ethanol extract was found to be particularly active in HCT116 human colon cancer cells at IC50 = 7.5  0.2 μg/ml after 48 h of incubation, a concentration that is only 3.5 times less effective than cisplatin (IC50 = 2.1 ± 0.09 μg/ml) under the same experimental conditions. The extract caused an arrest in the G2/M phase of the cell cycle with a consequent failure in mitosis. Using 2 x IC50 concentrations, a typical DNA fragmentation and activation of specific apoptotic proteins (caspase-3) was observed, suggesting apoptosis induction. Apoptosis was confirmed by the gradual increase in the expression levels of MDM2, p53, p21 and CyclinB1 proteins in the molecular analyses. These findings strongly suggest that the leaf extract of G. sokotensis contains active molecules that should be further evaluated for their anticancer properties. This plant may be used as a possible pharmaceutical supplement.

Giulio Lupidi a, Luca Avenali a, Massimo Bramucci a, Luana Quassinti a, Riccardo Pettinari b, Hala K. Khalife c, Hala Gali-Muhtasib d, Fabio Marchetti e, Claudio Pettinari b, -Synthesis, properties, and antitumor effects of a new mixed phosphine gold(I) compound in human colon cancer cells Claudio Pettinar 2013

The antineoplastic potential of a new stable mixed phosphine gold(I) complex containing tris(tert-butyl) phosphine (tBu3P) and bis(diphenylphosphino)ethene (dppet), namely [Au(tBu3P)(dppet)Cl], has been investigated in the human colon cancer HCT-116 cell line. The 31P NMR solution study, confirms the structural features observed in the solid state and, in addition, indicates partial formation of dinuclear cationic [Au(tBu3P)2]+ and [Au(dppet)2]+ species. The ionic character and strong Au–P bonds of this gold(I) species are similar to those of themost active antitumor gold compounds so far studied. The title compoundwas found to exhibit strong cytotoxicity, showing 85 fold greater toxicity than cisplatin (IC50 = 0.45 μM vs IC50 = 39.16 for cisplatin at 24 h) on the HCT-116 line. The cytotoxic effects were, at least partly,mediated by the induction of apoptotic cell death as evidenced by the sub-G1 cell accumulation, oligonucleosomal DNA fragmentation, caspase-3 activation and the release of cytochrome c from the mitochondria. The gold(I) compound showed little interaction with DNA measured through fluorescence quenching studies with calf thymus DNA. The inhibitory effect of the gold(I) compound on intracellular redox proteins has been also observed in pretreated HCT-116 cells. The compound was particularly effective in inhibiting thioredoxin reductase, that is likely responsible for the increased ROS production, and subsequent apoptosis induction via the mitochondrial pathway. © 2013 Elsevier Inc. All rights reserved.


ABSTRACT: Thymoquinone (TQ) is themain bioactive component isolated from Nigella sativa essential oil and seeds and has been used for the treatment of inflammations, liver disorders, arthritis, and is of great importance as a promising therapeutic drug for different diseases including cancer. This paper reports the first experimental evidence on binding of TQ to human "1-acid glycoprotein (AGP), an important drug-binding glycoprotein in human plasma, which affects pharmacokinetic properties of various therapeutic agents. The interaction of TQ with AGPhas been characterized by Fourier transform infrared (FTIR) and fluorescence spectroscopy, as well as by molecular docking experiments. FTIR spectroscopy showed that the binding of TQ to AGP slightly increases its thermal stability and shifts the existence of a molten globulelike state observed in a previous study to higher temperature. The binding constants Ka; the number of binding sites n; and the corresponding thermodynamic parameters G, H, and S at different temperatures were calculated through fluorescence spectroscopy. Fluorescence quenching experiments indicated that TQ binding involves hydrophobic interactions and to a lower extent hydrogen bonds, in agreement with molecular docking experiments. The data on binding ability of TQ to AGP represent basic information for the TQ pharmacokinetics such as drug metabolism and distribution in the body.

G. Lupidi a,1, A.Scire b,1, E.Camaioni c, K.H.Khalife a, G.DeSanctis a, F.Tanfani b, E.Damiani b,n Thymoquinone,apotentialtherapeuticagentof Nigella sativa, binds tositeIofhumanserumalbumin G. LUPIDI 2010

Thymoquinone(TQ)isthemainconstituentof Nigellasativa essentialoilwhichshowspromising in vitro and in vivo antineoplasticgrowthinhibitionagainstvarioustumorcelllines.Becauseoftheincreasing interest totestitinpre-clinicalandclinicalresearchesforassessingitshealthbenefits,wehereevaluate the interactionsbetweenTQandhumanserumalbumin(HSA),apossiblecarrierofthisdrug in vivo. BindingtoHSAwasstudiedusingdifferentspectroscopictechniques.Fouriertransforminfrared(FT-IR) and circulardichroism(CD)spectroscopiessuggestthattheassociationbetweenTQandHSAdoesnot affect thesecondarystructureofHSA.Usingfluorescencespectroscopy,onemoleofTQwasfound to bindonemoleofHSAwithabindingconstantof2.39 7 0.2104 M1. At251C (pH7.4),van’t Hoff’s enthalpyandentropythataccompanythebindingwerefoundtobe 10.24 kJ/mol1 and 45 J/mol1K1 respectively.ThethermodynamicanalysisoftheTQ-HSAcomplexformationshowsthat the bindingprocessisenthalpydrivenandspontaneous,andthathydrophobicinteractionsarethe predominantintermolecularforcesstabilizingthecomplex.Furthermore,displacementexperiments using warfarinandibuprofenindicatethatTQcouldbindtositeIofHSA,whichisalsoinagreement with theresultsofthemolecularmodelingstudy.

K. H. KHALIFE & G. LUPIDI Nonenzymatic reduction of thymoquinone in physiological conditions G. LUPIDI 2007

Thymoquinone (TQ) is the bioactive constituent of the volatile oil of Nigella sativa L. and has been shown to exert antioxidant antineoplastic and anti-inflammatory effects. During the study of its possible mechanism of action, we found that TQ reacts chemically (i.e. nonenzymatically) with glutathione (GSH), NADH and NADPH. A combination of liquid chromatography/UV–Vis spectrophotometry/Mass spectrometry analyses was used to identify the products of these reactions. The reaction that occur in physiological conditions indicates the formation of only two products, glutathionyl– dihydrothymoquinone after rapid reaction with GSH, and dihydrothymoquinone (DHTQ) after slow reaction time with NADH and NADPH. Measurement of the antioxidant activity of reduced compounds against organic radicals such as 2,20- azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) also revealed a potential scavenging activity for glutathionyl–dihydrothymoquinone similar to that of DHTQ. Under our experimental conditions, TQ shows lower scavenging activities than glutathionyl–dihydrothymoquinone and DHTQ; it is very interesting to observe that the reduced compounds apparently show an antioxidant capacity equivalent to Trolox. The results indicate a possible intracellular nonenzymatic metabolic activation of TQ dependent on GSH, NADH or NADPH that may represent a “cellular switch” able to modulate cellular antioxidant defences.

K.H. Khalife, G. Lupidi ⁎ Reduction of hypervalent states of myoglobin and hemoglobin to their ferrous forms by thymoquinone: The role of GSH, NADH and NADPH G. LUPIDI 2007

The reactivity of thymoquinone towards different redox states of hemoglobin and myoglobin in the presence of GSH, NADH, and NADPH was evaluated by optical spectral analysis. Thymoquinone reduces the ferryl forms (HbIV/MbIV) of both met-hemoglobin (HbIII) and metmyoglobin (MbIII) to oxy-hemoglobin (HbIIO2) and oxy-myoglobin (MbIIO2) under physiological conditions. The reaction is mediated by the intermediate quinone forms of TQ, that is, glutathionyl-dihydrothymoquinone (DHTQ-GS) and dihydrothymoquinone (DHTQ), formed from direct interaction of TQ with GSH or NADH (NADPH). In vitro incubation of oxidized human erythrocytes with TQ, DHTQ, and the GSH/TQ mixture reduces the intracellular met-Hb at different rates. In the present study, we report that TQ and its reduced derivatives can also prevent lipid peroxidation induced by the MbFeIII/H2O2 system. In this system, lipid peroxidation is induced by MbIV or a putative MbIV/·MbVI composite; it is plausible that the antioxidant function of TQ derivatives is related to their ability to reduce these oxidizing species. This is of particular biological significance, as natural quinones may participate in reducing processes that lead to recovery of hemoglobin and myoglobin during oxidative stress. © 2007 Elsevier B.V. All rights reserved.


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