Synergism between apple procyanidins and lysosomotropic drugs: potential in chemoprevention.
BACKGROUND
Procyanidins are apple constituents with potential in colon cancer chemoprevention.


METHODS
Human colon cancer derived metastatic cells (SW620), growing under standardized conditions, were exposed to procyanidins and lysosomotropic compounds. Growth, apoptosis and lysosomal integrity was determined using published methods.


RESULTS
Lysosomotropic drugs (MDL 72527, phenylalanine methylester and chloroquine) amplified procyanidin-induced growth inhibition and apoptosis in SW620 cells at non-cytotoxic concentrations. The improved toxicity of the drug combinations relies primarily on the enhancement of lysosomal membrane permeability.


CONCLUSIONS
Combinations with non-toxic concentrations of lysosomotropic compounds improve the anti-carcinogenic properties of apple procyanidins.
Seiler
Nikolaus
N
INSERM U682, Laboratory of Nutritional Cancer Prevention, IRCAD, 67091 Strasbourg, France. nikolaus.seiler@ircad.u-strasbg.fr
Chaabi
Mehdi
M
Roussi
Stamatiki
S
Gossé
Francine
F
Lobstein
Annelise
A
Raul
Francis
F
D000962:Antimalarials / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D002738:Chloroquine / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004357:Drug Synergism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D027845:Malus / Q000737:chemistry*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000962:Antimalarials; D000975:Antioxidants; D044946:Biflavonoids; D044945:Proanthocyanidins; C044445:MDL 72527; C034515:phenylalanine methyl ester; D010649:Phenylalanine; C017674:procyanidin; D002738:Chloroquine; D002392:Catechin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011700:Putrescine