Silibinin synergizes with mitoxantrone to inhibit cell growth and induce apoptosis in human prostate cancer cells
Article first published online: 17 JAN 2007
Copyright © 2006 Wiley-Liss, Inc.
International Journal of Cancer
Volume 120, Issue 9, pages 2028–2033, 1 May 2007
How to Cite
Flaig, T. W., Su, L.-J., Harrison, G., Agarwal, R. and Glodé, L. M. (2007), Silibinin synergizes with mitoxantrone to inhibit cell growth and induce apoptosis in human prostate cancer cells. Int. J. Cancer, 120: 2028–2033. doi: 10.1002/ijc.22465
- Issue published online: 28 FEB 2007
- Article first published online: 17 JAN 2007
- Manuscript Accepted: 11 OCT 2006
- Manuscript Received: 18 AUG 2006
- NIH. Grant Numbers: 5P30CA46934, NRSA T32 CA079446-06A1
- prostate cancer
The purpose of these experiments was to assess the synergistic activity of silibinin with chemotherapy agents in clinical use against prostate cancer. Silybin-phytosome, a commercially available formulation containing silibinin, has recently been studied in a phase I clinical trial. The silibinin doses used in the present study are clinically achievable based on the preliminary phase I data. DU145, PC-3 and LNCaP prostate cancer cells were seeded in 96-well plates in triplicate. Twenty-four hours later, silibinin (10, 20 and 40 μM) and either mitoxantrone or docetaxel were added to the designated wells. Seventy-two hours post-treatment, cell viability was determined with a tetrazolium-based assay. The combination index (CI) for determination of a synergistic effect was calculated, with values of <0.9 indicating synergy and values >1.1 antagonism. Apoptosis was also assessed using a luminescent assay after 72 hr of treatment with media alone, silibinin, mitoxantrone, or silibinin plus mitoxantrone. Silibinin showed a synergistic effect with mitoxantrone, as measured by reduction in cell viability. The CI values ranged from 0.413 to 2.650 for the combination of silibinin and mitoxantrone; in contrast, treatment with docetaxel and silibinin showed little or no synergy, with CI values of 0.898–4.469. In concordance with these findings, the addition of silibinin increased the level of apoptosis compared to mitoxantrone alone, particularly in the PC-3 cells. The combination of silibinin and mitoxantrone exhibits a pattern of synergy in reducing cell viability with increased apoptosis. These data are important in the planning of future clinical applications of silibinin. © 2007 Wiley-Liss, Inc.