The molecular mechanism by which the lipido-sterolic extract of Serenoa repens (LSESr, Permixon) affects prostate cells remains to be fully elucidated. In androgen-independent PC3 prostate cancer cells, the LSESr-induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC-1 dye to detect mitochondrial membrane potential. Cell membrane lipid composition was evaluated by thin layer chromatography and gas chromatographic analysis. Akt phosphorylation was analyzed by Western blotting and cellular ultrastructure through electron microscopy. LSESr (12.5 and 25 microg/ml) administration exerted a biphasic action by both inhibiting proliferation and stimulating apoptosis. After 1 h, it caused a marked reduction in the mitochondrial potential, decreased cholesterol content and modified phospholipid composition. A decrease in phosphatidylinositol-4,5-bisphosphate (PIP2) level was coupled with reduced Akt phosphorylation. After 24 h, all of these effects were restored to pre-treatment conditions; however, the saturated (SFA)/unsaturated fatty acid (UFA) ratio increased, mainly due to a significant decrease in omega 6 content. The reduction in cholesterol content could be responsible for both membrane raft disruption and redistribution of signaling complexes, allowing for a decrease of PIP2 levels, reduction of Akt phosphorylation and apoptosis induction. The decrease in omega 6 content appears to be responsible for the prolonged and more consistent increase in the apoptosis rate and inhibition of proliferation observed after 2-3 days of LSESr treatment. In conclusion, LSESr administration results in complex changes in cell membrane organization and fluidity of prostate cancer cells that have progressed to hormone-independent status.

Lipido-Sterolic Extract of Serenoa repens (LSESr, Permixon (R)) Treatment Affects Human Prostate Cancer Cell Membrane Organization / Petrangeli, Elisa; Lenti, Luisa; Buchetti, Barbara; Chinzari, P; Sale, Patrizio; Salvatori, Luisa; Ravenna, Linda Ester; Lococo, E; Morgante, Emanuela; Russo, Matteo Antonio; Frati, Luigi; DI SILVERIO, Franco; Russo, Matteo Antonio. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 219(1):(2009), pp. 69-76. [10.1002/jcp.21648]

Lipido-Sterolic Extract of Serenoa repens (LSESr, Permixon (R)) Treatment Affects Human Prostate Cancer Cell Membrane Organization

PETRANGELI, Elisa;LENTI, Luisa;BUCHETTI, Barbara;SALE, PATRIZIO;SALVATORI, Luisa;RAVENNA, Linda Ester;MORGANTE, Emanuela;RUSSO, Matteo Antonio;FRATI, Luigi;DI SILVERIO, Franco;RUSSO, Matteo Antonio
2009

Abstract

The molecular mechanism by which the lipido-sterolic extract of Serenoa repens (LSESr, Permixon) affects prostate cells remains to be fully elucidated. In androgen-independent PC3 prostate cancer cells, the LSESr-induced effects on proliferation and apoptosis were evaluated by counting cells and using a FACScan cytofluorimeter. PC3 cells were stained with JC-1 dye to detect mitochondrial membrane potential. Cell membrane lipid composition was evaluated by thin layer chromatography and gas chromatographic analysis. Akt phosphorylation was analyzed by Western blotting and cellular ultrastructure through electron microscopy. LSESr (12.5 and 25 microg/ml) administration exerted a biphasic action by both inhibiting proliferation and stimulating apoptosis. After 1 h, it caused a marked reduction in the mitochondrial potential, decreased cholesterol content and modified phospholipid composition. A decrease in phosphatidylinositol-4,5-bisphosphate (PIP2) level was coupled with reduced Akt phosphorylation. After 24 h, all of these effects were restored to pre-treatment conditions; however, the saturated (SFA)/unsaturated fatty acid (UFA) ratio increased, mainly due to a significant decrease in omega 6 content. The reduction in cholesterol content could be responsible for both membrane raft disruption and redistribution of signaling complexes, allowing for a decrease of PIP2 levels, reduction of Akt phosphorylation and apoptosis induction. The decrease in omega 6 content appears to be responsible for the prolonged and more consistent increase in the apoptosis rate and inhibition of proliferation observed after 2-3 days of LSESr treatment. In conclusion, LSESr administration results in complex changes in cell membrane organization and fluidity of prostate cancer cells that have progressed to hormone-independent status.
2009
01 Pubblicazione su rivista::01a Articolo in rivista
Lipido-Sterolic Extract of Serenoa repens (LSESr, Permixon (R)) Treatment Affects Human Prostate Cancer Cell Membrane Organization / Petrangeli, Elisa; Lenti, Luisa; Buchetti, Barbara; Chinzari, P; Sale, Patrizio; Salvatori, Luisa; Ravenna, Linda Ester; Lococo, E; Morgante, Emanuela; Russo, Matteo Antonio; Frati, Luigi; DI SILVERIO, Franco; Russo, Matteo Antonio. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 219(1):(2009), pp. 69-76. [10.1002/jcp.21648]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/365170
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