BIPHASIC RESPONSES TO FALCARINOL
IN CELL CULTURES
JETTE FEVEILE YOUNG
DEPARTMENT OF FOOD SCIENCE
AARHUS
UNIVERSITY OF AARHUS, DENMARK
AA R H U S UNIVERSITET
Faculty of Agricultural Sciences
HYPOTHESIS
HEALTH-EFFECTS
POSITIVE HEALTH EFFECTS OF FRUIT
AND VEGETABLES
S G CO OU S S G
SINGLE COMPOUNDS INVESTIGATED
VITAMINS
MINERALS
FIBRES
CAROTENOIDS
PHENOLIC ACIDS
FLAVONOIDS
NEW HYPOTHESIS
SEVERAL COMPOUNDS IN COMBINATION
LESS ABUNDANT CO-OCCURING COMPOUNDS
HIGHLY BIOACTIVE COMPOUNDS
PRESENCE IN HIGHLY CONSUMED FRIUT AND
VEGETABLES
BIOAVAILABLE OR ACTIVE IN GI TRACT
SIGNALLING MOLECULES
FALCARINOL AND FALCARINDIOL
LESS ABUNDANT
HIGHLY BIOACTIVE
ANTI-INFLAMATORY
CYTOTOXIC
ANTI-PLATELET-
AGGREGATORY
IMMUNE-STIMULATING
APIACEAE FAMILY
CARROTS
CELERY
PARSLEY
GI OR POST ABSORPTION
EXPERIMENTS ON CACO2 CELLS
PROLIFERATION
APOPTOSIS
CELL DETACHMENT
DNA ALTERATIONS
EXPERIMENTS ON MUSCLE CELLS
PROLIFERATION
200 **
*
TAL CEL COUNNT
150
NTROL
LL
% OF CON
100
O
50
TOT
*** ***
0
0 0.5 1 10 20 50 100
FALCARINOL, μM
CASPASE 3
CASPASE-3 EXPRESSING CELLS
82
TIME ***
80
24 h
72 h
L
% OF TOTAL
PASE-3
8
6
CASP
F
4 * *
2
*
0
0 0.1
01 1 10 100
FALCARINOL, μM
CASPASE 3
CELL DETACHMENT AND CASPASE-3
80
TIME
c
24 h
48 h
72 h
60
CASPASE-3, % OF TOTAL
c c
b
40
b
b
d
d
C
20
d
a
a a
0
Control Total cells Detached cells Adherent cells
50 mM Falcarinol
DNA STRAND BREAKS
400 TIME ******
EAKS
24 h ***
72 h
DNA STRAND BRE
300
***
200
** ***
*
100
A
*
* *
**
0
0 0.5 1 10 20 50 100H2O2
H2O2
FALCARINOL, μM
GI OR POST ABSORPTION
EXPERIMENTS ON CACO2 CELLS
EXPERIMENTS ON MUSCLE CELLS
HSP70 AND HO1
GPX
ROS
PRIMARY MYOTUBE FORMATION
j
MUSCLE CELL CULTURE
MOST ABUNDANT CELL TYPE (40%)
STRESS AT PHYSICAL EXERCISE
SUPRESSING AND ACCELERATING
STRESSOR: 100 μM H2O2
INTRACELLULAR ROS
FALCARINOL (μM)
140 100
50
120
25
SCENCE
100 12.5
6.3
80 3.1
FLOURES
1.6
60 C
40
F
20
0
0 5000 10000 15000 20000
TIME (S)
HSP AND GPX m-RNA RESPONSE
FALCARINOL
10
HSP70
HO1
NGE)
b b b GPX
RNA (FOLD CAHN
c
1 a
d
b
c c
m-R
b
b c c
0.1
0 10 20 30 40 50 60
FALCARINOL (μM)
THANKS TO
AT THE ROWETT RESEARCH INSTITUTE
CHARLES BESTWICK
SUSAN DUTHIE
GARRY DUTHIE
AT AARHUS UNIVERSITY
LARS P. CHRISTENSEN
NIELS OKSBJERG
PETER THEIL