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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Cherry extract-
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EtOH
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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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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
