Amelioration of the cytotoxic effects of chemotherapeutic agents by grape seed proanthocyanidin extract.
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 microg/ml) with or without GSPE (25 microg/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 Bcl-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 Bcl-2 expression.
Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha 68198-6395, USA. ssjoshi@unmc.edu
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Joshi
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Kuszynski
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Benner
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Bagchi
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Bagchi
D000872:Anthocyanins / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D004847:Epithelial Cells; D005434:Flow Cytometry; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology; D044945:Proanthocyanidins; D019685:Rosales / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry*
D000872:Anthocyanins; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000975:Antioxidants; D044945:Proanthocyanidins; C013221:proanthocyanidin; D003520:Cyclophosphamide; C011272:perfosfamide; D015255:Idarubicin