Chemotherapeutic activity of silymarin combined with doxorubicin or paclitaxel in sensitive and multidrug-resistant colon cancer cells

Valentina Colombo, Monica Lupi, Francesca Falcetta, Daniele Forestieri, Maurizio D'Incalci, Paolo Ubezio

Research output: Contribution to journalArticle

Abstract

Purpose: The milk thistle extract silymarin, alone or in combined chemotherapy, is now under investigation in anticancer research, with particular interest for its possible employ in the treatment of chemoresistant tumours. So far, the consequences of a silymarin pre-treatment have not been thoroughly investigated. We studied whether silymarin pre-treatment synergized with chemotherapy, exploring the dose-dependence of the interaction in sensitive and multidrug-resistant cells. Methods: We studied cell cycle perturbations induced by silymarin in two colon carcinoma cell lines, LoVo and the multidrug-resistant isogenic LoVo/DX. Synergism/additivity/antagonism of silymarin-doxorubicin silymarin-paclitaxel combined treatments were evaluated by isobologram/ combination index analysis, in the whole spectrum of active and sub-active concentrations of all drugs. The mechanisms of silymarin interaction with the other drugs were investigated by measuring drug uptake and cell cycle perturbations. Results: Silymarin had similar antiproliferative activity against both cell lines. Pre-treatment with low silymarin concentrations synergised with both doxorubicin and paclitaxel in LoVo but not in LoVo/DX. Higher silymarin concentrations were additive with doxorubicin and paclitaxel in both cell lines. Silymarin favourably interfered with uptake and cell cycle effects of the chemotherapeutics in LoVo but not in LoVo/DX. Conclusion These findings confirm activity of silymarin against colon carcinoma, including multidrug-resistant types, at relatively high but clinically achievable concentrations. In view of its low toxicity, two schedules based on low-and high-dose silymarin pre-treatment might offer a valuable option for combined treatment.

Original languageEnglish
Pages (from-to)369-379
Number of pages11
JournalCancer Chemotherapy and Pharmacology
Volume67
Issue number2
DOIs
Publication statusPublished - Feb 2011

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Keywords

  • Combination chemotherapy
  • Drug uptake
  • Flow cytometry
  • Multidrug resistance
  • Silymarin
  • Synergism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology (medical)
  • Pharmacology
  • Toxicology

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