Modulation by polyamines of apoptotic pathways triggered by procyanidins in human metastatic SW620 cells.
We showed previously that inhibition of polyamine catabolism with the polyamine oxidase inhibitor MDL 72527 (MDL) potentiates the apoptotic effects of apple procyanidins (Pcy) in SW620 cells. Here we report that Pcy caused an activation of the intrinsic apoptotic pathway through enhanced polyamine catabolism and mitochondrial membrane depolarization. MDL in the presence of Pcy caused a profound intracellular depletion of polyamines and exerted a protective effect on mitochondrial functions. MDL potentiation of Pcy-triggered apoptosis was reversed by addition of exogenous polyamines. In addition, MDL in combination with Pcy activated the extrinsic apoptotic pathway through enhanced TRAIL-death receptor (DR4/DR5) expression. Potentiation of Pcy-triggered apoptosis by MDL was inhibited when cells were exposed to specific inhibitors of DR4/DR5. These data indicate that the depletion of intracellular polyamines by MDL in the presence of Pcy caused a switch from intrinsic to extrinsic apoptotic pathways in human colon cancer-derived metastatic cells.
Maldonado-Celisa
M E
ME
INSERM U682, Laboratory of Nutritional Cancer Prevention, Bat. IRCAD, 1, Place de l'Hôpital, 67000 Strasbourg, France.
Roussia
S
S
Foltzer-Jourdainne
C
C
Gossé
F
F
Lobstein
A
A
Habold
C
C
Roessner
A
A
Schneider-Stock
R
R
Raul
F
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009362:Neoplasm Metastasis; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D011073:Polyamines / Q000378:metabolism*; D044945:Proanthocyanidins / Q000494:pharmacology*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism; D013095:Spermidine / Q000494:pharmacology; D000097667:Polyamine Oxidase
D004791:Enzyme Inhibitors; D006655:Histone Deacetylases; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D044945:Proanthocyanidins; D011700:Putrescine; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D013095:Spermidine; D000097667:Polyamine Oxidase; C044445:MDL 72527