Antiproliferative effect of silybin on gynaecological malignancies: Synergism with cisplatin and doxorubicin

G. Scambia, R. De Vincenzo, F. O. Ranelletti, P. Benedetti Panici, G. Ferrandina, G. D'Agostino, A. Fattorossi, E. Bombardelli, S. Mancuso

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to test the antiproliferative activity of silybin, a flavonoid, on human ovarian and breast cancer cell lines. Since flavonoids are thought to act through Type II oestrogen binding sites (Type II EBS), silybin binding to Type II EBS was also examined. Silybin, used in concentrations from 0.1 to 20 μM, exerted a dose-dependent growth inhibitory effect on OVCA 433, A2780 parental and drug-resistant ovarian cancer cells, and MCF-7 doxorubicin (DOX)-resistant breast cancer cells (IC50 = 4.8-24 μM). Both L and D diastereoisomers of silybin were effective in inhibiting A2780 WT cell growth (IC50 = 14 and 20 μM, respectively). Flow cytometry revealed that silybin decreased the percentage of cells in the S and G2-M phases of the cell cycle with a concomitant increase in cells in the G0-G1 phase. Silybin was able to compete with [3H]E2 for nuclear but not cytosolic Type II EBS. Its affinity parallels its efficacy in inhibiting cell proliferation. Furthermore, silybin (0.1 and 1 μM) potentiates the effect of cisplatin (CDDP) (0.1-1 μg/ml) in inhibiting A2780 WT and CDDP-resistant cell growth. Similar results were obtained on MCF-7 DOX-resistant cells when silybin (0.1 μM) was associated with doxorubicin (0.1-10 μg/ml). As assessed by the Berembaum isobole method, the effect of silybin-CDDP and silybin-DOX combinations results in a synergistic action. Using the 'stem cell assay' described by Hamburger and Salmon [Science 1977, 197, 461-463], we found that silybin exerted a dose-dependent inhibition of clonogenic efficiency of cells derived from three ovarian tumours (IC50 = 7.4, 4 and 6.4 μM, respectively). Since CDDP and DOX are the two most commonly used drugs for gynaecological tumours, the clinical application of silybin is currently under investigation in our institute.

Original languageEnglish
Pages (from-to)877-882
Number of pages6
JournalEuropean Journal of Cancer
Volume32
Issue number5
DOIs
Publication statusPublished - May 1996

Keywords

  • Ovarian and breast cancer
  • Silybin
  • Synergism with CDDP and DOX

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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