Modulation by polyamines of apoptotic pathways triggered by procyanidins in human metastatic SW620 cells

• Published in: Cellular and molecular life sciences : CMLS Vol. 65; no. 9; pp. 1425 - 1434
• Main Authors: Maldonado-Celis, M. E, Roussi, S, Foltzer-Jourdainne, C, Gossé, F, Lobstein, A, Habold, C, Roessner, A, Schneider-Stock, R, Raul, F
• Format: Journal Article
• Language: English
• Published: Basel Basel : SP Birkhäuser Verlag Basel 01-05-2008; SP Birkhäuser Verlag Basel; Springer Nature B.V; Springer Verlag
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line, Tumor; Cellular biology; Colonic Neoplasms - enzymology; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Environmental Sciences; Enzyme Inhibitors - pharmacology; Enzymes; flavonoids; histone deacetylase; Histone Deacetylases - metabolism; Humans; Life Sciences; MDL 72527; Membrane Potential, Mitochondrial - drug effects; Metastasis; Mitochondria; Neoplasm Metastasis; Oxidoreductases Acting on CH-NH Group Donors - antagonists & inhibitors; polyamine; Polyamine Oxidase; Polyamines - metabolism; polyphenols; Proanthocyanidins - pharmacology; Putrescine - analogs & derivatives; Putrescine - pharmacology; Receptors, TNF-Related Apoptosis-Inducing Ligand - antagonists & inhibitors; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Research Article; Spermidine - pharmacology; TRAIL death receptors; TRAIL death receptors; polyamine; polyphenols; mitochondria; flavonoids; MDL 72527; histone deacetylase; Apoptosis
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-008-8023-4

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.