title: Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: an overview.
abstract: A large number of investigations have demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and degenerative diseases including cardiovascular dysfunctions, acute and chronic stress, gastrointestinal distress, neurological disorders, pancreatitis, various stages of neoplastic processes and carcinogenesis including detoxification of carcinogenic metabolites. GSP exhibited potent free radical scavenging abilities in both in vitro and in vivo models. GSP exerted significant in vivo protection against structurally diverse drug and chemical-induced hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity and spleentoxicity. GSP also protected against idarubicin and 4-hydroxyperoxy-cyclophosphamide-induced cytotoxicity toward human normal liver cells. GSP exhibited selective cytotoxicity toward selected human cancer cells, while enhancing the growth and viability of normal cells. GSP exhibited potent modulatory effects of pro-apoptotic and apoptotic regulatory bcl-XL, p53, c-myc, c-JUN, JNK-1 and CD36 genes. Long-term exposure to GSP may serve as a novel chemoprotectant against three stages of DMN-induced liver carcinogenesis and tumorigenesis including initiation, promotion and progression. GSP may selectively protect against oxidative stress, genomic integrity and cell death patterns in vivo. These results demonstrate that GSP may serve as a novel therapeutic intervention against carcinogenesis.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA; Research & Development Division, Cepham Inc., Piscataway, NJ, USA. Electronic address: debasisbagchi1@gmail.com.
authors.forename: Debasis
authors.initials: D
authors.lastname: Bagchi
authors.affiliation: Research & Development Division, Cepham Inc., Piscataway, NJ, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.affiliation: Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: Harry G
authors.initials: HG
authors.lastname: Preuss
authors.affiliation: Research & Development Division, Cepham Inc., Piscataway, NJ, USA.
authors.forename: Manashi
authors.initials: M
authors.lastname: Bagchi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D056604:Grape Seed Extract / Q000627:therapeutic use*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000378:metabolism; D044945:Proanthocyanidins / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016166:Free Radical Scavengers; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D009363:Neoplasm Proteins; D044945:Proanthocyanidins
keywords: 4-Hydroxyperoxycyclophosphamide; Amiodarone; Apoptosis; Cancer; DNA damage; Dimethylnitrosamine; Doxorubicin; Free radicals; Grape seed proanthocyanidins; Idarubicin; Multiorgan toxicity; Necrosis; Vitamins C, E and β-carotene