Marine compounds as promising anti-cancer agents

Marine compounds as promising anti-cancer agents

Marine compounds as
promising anti-cancer agents
Laboratoire de Biologie
Moléculaire et Cellulaire
du Cancer of
Dr Marc DIEDERICH
Hôpital Kirchberg Luxembourg
• marine invertebrate extracts
from the NCI (USA) and from Fiji
• bacterial strains from marine sediment
• algal strains from the Culture Collection of Algae and
Protozoa (Scottish Association for Marine Sciences)
Inhibition of NF-kB binding
Folmer et al, Biochem Pharmacol. 78 (2009) 592–606.
Heteronemin isolated from
Porifera Hyrtios
Heteronemin, first discovered from Hyrtios erecta by the research group of Wells and coworkers , was isolated from the Fijian sponge Porifera Hyrtios, it’s a colourless oil soluble
in methanol and DMSO.
This compound exhibited antimycobacterial activity against M. tubercolosis H37Rv with a
MIC value of 6.25 mg/ml. An antitubercular activity was reported in litterature.
Heteronemin has been shown to be a Protein Farnesyl Transferase Inhibitor by Ledroit
and co-workers.
Heteronemin – NF-κ
κB pathway
Schumacher, M.*; Cerella, C.*; Eifes, S.*; Chateauvieux, S.; Morceau, F.; Jaspars, M.; Dicato, M.; Diederich, M.
Biochem Pharmacol 2010, 79, 610
Heteronemin – NF-κ
κB pathway
Collaboration with J.-P. Becker and M. Prévost
apoptotic signalling
damaging
stimuli
cell, DNA
damage,
chemotherapics
GSH
extrusion
Ca2+
calpains
BAK/BAX
activation
cytochrome c
release
Apoptosome
formation
Caspase-9
activation
stress
nuclear
fragmentation
Caspase-3
activation
DNA digestion
chromatin
condensation
t-Bid
cytoskeletral
distruction
death
receptor
stimulation
death
domain
inhibition
DISC
formation
Caspase-8
activation
mitochondria
psi loss
PS exposure
rescue (normally viable cells)
cells death
Modified from Coppola and Ghibelli, Biochem Soc Trans. 2000,28(2):56-61.
gracilins (1-6), tetrahydroaplysulphurin-1 (7), 3′-norspongiolactone (8), spongiolactone (9)
Epigenetic drugs
HDACs
HATs
DNMTs
Total HDAC
(class I & II)
Total HAT
Total DNMT
Class I
HDAC1
DNMT1
HDAC2
DNMT3A
HDAC3
DNMT3B
HDAC8
Class IV
Class II
HDAC11
HDAC6
HDAC10
SIRT1
Class III
SIRT2
SIRT3
Collaborations?
LBMCC is financed by …
Foundation “Recherche Cancer et Sang”
“Recherches Scientifiques Luxembourg” asbl
National Research Fund – Luxembourg
Ministry of Research - Luxembourg
FNRS Télévie – Luxembourg
Action LIONS “Vaincre le Cancer” asbl
An “Häerz fir Kriibskrank Kanner” asbl
Stiftung zur Förderung der deutsch-luxemburgischen Zusammenarbeit auf dem
Gebiet der Wissenschaften
LBMCC Hôpital Kirchberg 2008
http://www.lbmcc.lu
[email protected]