Amelioration of the Cytotoxic Effects of Chemotherapeutic Agents by Grape Seed Proanthocyanidin Extract

Shantaram S. Joshi, Charles A. Kuszynski, Eric J. Benner, Manashi Bagchi, Debasis Bagchi

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Anticancer chemotherapeutic agents are effective in inhibiting growth of cancer cells in vitro and in vivo, however, toxicity to normal cells is a major problem. In this study, we assessed the effect of a novel IH636 grape seed proanthocyanidin extract (GSPE) to ameliorate chemotherapy-induced toxic effects in cultured Chang epithelial cells, established from nonmalignant human tissue. These cells were treated in vitro with idarubicin (Ida) (30 nM) or 4-hydroxyperoxycyclophosphamide (4HC) (1 μg/ml) with or without GSPE (25 μg/ml). The cells were grown in vitro and the growth rate of the cells was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; thiazolyl blue] assay. Our results showed that GSPE decreased the growth inhibitory and cytotoxic effects of Ida as well as 4HC on Chang epithelial cells in vitro. Because these chemotherapeutic agents are known to induce apoptosis in the target cells, we analyzed the Chang epithelial cells for apoptotic cell population by flow cytometry. There was a significant decrease in the number of cells undergoing apoptosis following treatment with GSPE. We also found increased expression of the anti-apoptotic protein Bc1-2 in GSPE-treated cells using western blot techniques. Thus, these results indicate that GSPE can be a potential candidate to ameliorate the toxic effects associated with chemotherapeutic agents and one of the mechanisms of action of GSPE includes upregulation of Bc1-2 expression.

Original languageEnglish (US)
Pages (from-to)563-570
Number of pages8
JournalAntioxidants and Redox Signaling
Volume1
Issue number4
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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