catarina duarte / design of nutraceuticals targeting cancer
DESCRIPTION
Presentation given by Catarina Duarte from the Chemistry and Biology Technological Institute (New University of Lisbon) in the framework of the Emergence Forum Barcelona Biocat organized the Barcelona Emergence Forum (April 10-11th, 2014, Congress Palace, Montjuïc) supported by the TRANSBIO SUDOE, a translational cooperation project dedicated to innovation in life sciences in South-West Europe. The Barcelona Emergence Forum contributed to bringing together Academics, Companies, Investment Entities, Technology Platforms and Technology Transfer Offices from Spain, France and Portugal to set up collaborative projects on Human Health & Agro-food Innovation. More information at: http://www.b2match.eu/emergenceforum2014TRANSCRIPT
Development of Nutraceuticals targeting cancer
Catarina DuarteFood & Health Unit
Nutraceuticals and controlled Delivery LabIBET/ ITQB-UNLOeiras, Portugal
�Green Processes for developing health promoting products
Extraction /Fraccionation of Natural Compounds
Research interests:
Formulation – particle formation, encapsulation and
impregnation
�Characterization and pre-clinical Bioactivity evaluation of bioproducts
Chemical, enzymatic and cell-based assays
Food&Health Unit Nutraceuticals and Controlled Delivery Lab
� POH was detected in
10%EtOH and 20%EtOH
extracts
Serra et al. (2010) J Supercri. Fluids, 55, 184-191
Sweet cherriesDevelopment of POH-rich extracts
� Application of High Pressure Technology for the development of natural extracts
rich in perillyl alcohol (POH)
Raw material:
Sweet cherry culls
(Saco variety)
POH
96h
�Only two extracts (10%EtOH and 20%EtOH) inhibited cancer cell growth in a
time dependent manner and this effect is related with the presence of Perillyl
Alcohol
� Cherry extracts induced cell cycle arrest in a different cell cycle checkpoint
than doxorrubicin suggesting that they can be used in combination with the
drug in chemotherapy
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Control 4h 24h 48h 72h 96h
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Cherry extract-
10% EtOH
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Control 4h 24h 48h 72h 96h
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10%
EtOH
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EtOH
40%
EtOH
60%
EtOH
80%
EtOH
100%
EtOH
CO2
Antiproliferative effect on HT29 cells (human colorectal cancer cell line)• Cell cycle analysis
Controlo
10% EtOH
20% EtOH
• Cell viability after 24, 48, 72 and 96h of proliferation
Serra et al. (2010) J Supercrit. Fluids, 55, 184-191
Serra et al. (2011) J Supercrit. Fluids,55 1007-10131st prize: “Inovation and Develo+ment of Products and Services” category
Sweet cherriesDevelopment of POH-rich extracts
Minutes
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4500Detector 1-280nmLaranja (2) TS Ago2913075.dat
Detector 1-280nmLaranja (3) TS Ago2913076.dat
Detector 1-280nmLaranja (4) TS Ago2913077.dat
Detector 1-280nmLaranja Dil 1:10Jul2413094.dat
Sinensetin
Nobiletin
Tangeretin
� Process: CO2+ EtOH (80:20 v/v); P=25MPa; T=323K; t=60min.
Tangeretina
Nobiletin
Sinensetin
Inês Silva (2013), Tese de mestrado
Citrus peelsDevelopment of PMF-rich extracts
� Application of Supercritical Fluid Technology for the development of natural extracts
rich in polymetoxylated flavones (PMF)
� Sinensetin, tangeritin and nobiletin were
identified in citrus pell extracts.
Raw material:
Orange peels(by-products of fruit juice
production)
Induction of apoptosis on HT29 cell spheroids
Control Citrus extract
(Red: viable cells; Green: apoptotic cells)
Cell viability• 2D model
� Orange extract inhibited the proliferation of
HT29 cells (antiproliferative effect was
dependent on spheroid size).
� Orange extract induced apoptosis in HT29
spheroids(apoptotic cells are mainly located
on the surface of the spheroid).
• 3D model
Cell monolayer Cell spheroids with different sizes
Antiproliferative effect on HT29 cells (human colorectal cancer cell line)
Inês Silva (2013), Master thesis
Citrus peelsDevelopment of PMF-rich extracts
Opuntia ficus-indicaDevelopment of terpene-rich extracts
Raw material:
Opuntia ficus-indica(by-products of fruit juice production)
� Process: CO2+ EtOH+ H2O mixtures; P=20MPa; T=313K; t=180min.
� Application of Pressurized Liquid Extracton for the development
of natural extracts rich in terpenes
fried lup #1 #2 #3 #4 #5 #6 #7 #8 #9 #10 fried lup #1 #2 #3 #4 #5 #6 #7 #8 #9 #10
Terpene
detection by TLC
� Opuntia extracts obtained with mixtures of CO2 and
EtOH presented high terpene content
� Opuntia extract obtained with CO2:EtOH (60:40v/v) mixture (PLE2) presented the highest
antiproliferative effect. This effect is probably due to the presence of terpenes.
� PLE-2 extracts increased drug sensitivity on HT29 dx cell population cells .
Antiproliferative effect on HT29 cells (human colorectal cancer cell line)
• Cell viability after 24 h of proliferation
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Ce
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ntr
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Doxorubicin (µM)
Doxorubicin in HT29 dx
Doxorubicin in HT29
PLE-2 + Doxo in HT29 dx
• Chemosensitization effect in a drug resistant cell sub-
population (HT29 dx)
Joana Poejo(2014), Master thesis
Opuntia ficus-indicaDevelopment of terpene-rich extracts
e-mail: [email protected];
http://www.itqb.unl.pt/labs/nutraceuticals-and-delivery
www.ibet.pt
Laboratório de Nutracêuticos e
Libertação Controlada
Oeiras, Portugal