Antiproliferative and pro-apoptotic activity of novel phenolic derivatives of resveratrol

P. Nigro, E. Bloise, M. C. Turco, A. Skhirtladze, P. Montoro, C. Pizza, S. Piacente, M. A. Belisario

Research output: Contribution to journalArticlepeer-review

Abstract

Gloriosaols A-C, isolated from Yucca gloriosa (Agavaceae), are novel phenolic compounds structurally related to resveratrol. In the present study, we show that gloriosaols possess antiproliferative and pro-apoptotic activity on tumor cells of different histogenetic origin and that their cell growth inhibition potential is higher than that of resveratrol. Despite the close similarities in their structure, gloriosaols A-C exhibited different antiproliferative potency, as the EC50 ascending order is: gloriosaol C, gloriosaol A, gloriosaol B. Further mechanisms of gloriosaol C cytotoxicity were elucidated in detail in U937 cells, the most sensitive of the cell lines tested. The effect of gloriosaol C on cell growth turned out to be strongly dependent upon the concentration. Gloriosaol C doses lower than the EC50 value (8 μM) blocked the cell cycle in G0/G1, with a concurrent decrease in the number of cells in the G2/M phases of the cell cycle. At higher doses, this arrest overlaps with the occurrence of apoptosis and necrosis. In the 10-25 μM range of doses, gloriosaol C caused cell death mainly by apoptosis, as measured by hypodiploidia induction, phosphatidyl serine externalization and disruption of mitochondrial transmembrane potential. A switch in the mode of death from apoptosis to necrosis occurred at doses of gloriosaol C higher than 30 μM. Gloriosaol C was found to induce production of reactive species dose-dependently, but also to counteract their elevation in stressed cells. Thus, the different fate of cells, that is cell cycle arrest or cell death, in response to different doses of gloriosaol C might be related to the extent of induced oxidative stress.

Original languageEnglish
Pages (from-to)873-883
Number of pages11
JournalLife Sciences
Volume81
Issue number11
DOIs
Publication statusPublished - Aug 23 2007

Keywords

  • Apoptosis
  • Cell cycle
  • Phenolic compounds
  • Reactive oxygen species (ROS)
  • Resveratrol

ASJC Scopus subject areas

  • Pharmacology

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