Lipido-sterolic extract of Serenoa repens (LSESr, Permixon®) treatment affects human prostate cancer cell membrane organization

E. Petrangeli, L. Lenti, B. Buchetti, P. Chinzari, P. Sale, L. Salvatori, L. Ravenna, E. Lococo, E. Morgante, A. Russo, L. Frati, F. Di Silverio, M. A. Russo

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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 evaluatedbycounting cells and usingaFACScan cytofluorimeter. PC3 cells were stained with JC-1 dye todetect 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 μg/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 ω6 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 ω6 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.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalJournal of Cellular Physiology
Volume219
Issue number1
DOIs
Publication statusPublished - Apr 2009

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Petrangeli, E., Lenti, L., Buchetti, B., Chinzari, P., Sale, P., Salvatori, L., Ravenna, L., Lococo, E., Morgante, E., Russo, A., Frati, L., Di Silverio, F., & Russo, M. A. (2009). Lipido-sterolic extract of Serenoa repens (LSESr, Permixon®) treatment affects human prostate cancer cell membrane organization. Journal of Cellular Physiology, 219(1), 69-76. https://doi.org/10.1002/jcp.21648