Grape seed proanthocyanidins (GSPs) inhibit the growth of cervical cancer by inducing apoptosis mediated by the mitochondrial pathway

• Published in: PloS one 2014-09, Vol.9 (9), p.e107045-e107045
• Main Authors: Chen, Qing, Liu, Xiao-Fang, Zheng, Peng-Sheng
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; BAK protein; bcl-2 Homologous Antagonist-Killer Protein - agonists; bcl-2 Homologous Antagonist-Killer Protein - genetics; bcl-2 Homologous Antagonist-Killer Protein - metabolism; Bcl-2 protein; Biochemistry; Biological activity; Biology and Life Sciences; Breast cancer; Cancer; Cancer prevention; Cancer therapies; Caspase; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; Cell cycle; Cell growth; Cell Line, Tumor; Cervical cancer; Cervix; Chemotherapy; Cold; Colorectal cancer; Developing countries; Drinking water; Female; Gene Expression Regulation, Neoplastic; Grape Seed Extract - pharmacology; Growth; Hospitals; Humans; Immunoglobulins; Kinases; LDCs; Lung cancer; Medical research; Medicine and Health Sciences; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mice; Mice, Nude; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Molecular biology; Pancreatic cancer; Pharmacology; Phytochemicals; Proanthocyanidins; Proanthocyanidins - pharmacology; Proteins; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reproductive health; Seeds; Signal Transduction - drug effects; Transplantation, Heterotopic; Tumor Burden - drug effects; Tumors; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Xenograft Model Antitumor Assays
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107045

Grape seed proanthocyanidins (GSPs), a biologically active component of grape seeds, have been reported to possess a wide array of pharmacological and biochemical properties. Recently, the inhibitory effects of GSPs on various cancers have been reported, but their effects on cervical cancer remain unclear. Here, we explored the effect of GSPs on cervical cancer using in vitro and in vivo models. In vitro, the treatment of HeLa and SiHa cells with GSPs resulted in a significant inhibition of cell viability. Further investigation indicated that GSPs led to the dose-dependent induction of apoptosis in cancer cells. The underlying mechanism was associated with increased expression of the pro-apoptotic protein Bak-1, decreased expression of the anti-apoptotic protein Bcl-2, the loss of mitochondrial membrane potential, and the activation of caspase-3, suggesting that GSPs induced cervical cancer cell apoptosis through the mitochondrial pathway. In addition, the administration of GSPs (0.1%, 0.2%, and 0.4%, w/v) as a supplement in drinking water significantly inhibited the tumor growth of HeLa and SiHa cells in athymic nude mice, and the number of apoptotic cells in those tumors was also increased significantly. Taken together, our studies demonstrated that GSPs could inhibit the growth of cervical cancer by inducing apoptosis through the mitochondrial pathway, which provides evidence indicating that GSPs may be a potential chemopreventive and/or chemotherapeutic agent for cervical cancer.