RRC ID 56035
著者 Czauderna C, Palestino-Dominguez M, Castven D, Becker D, Zanon-Rodriguez L, Hajduk J, Mahn FL, Herr M, Strand D, Strand S, Heilmann-Heimbach S, Gomez-Quiroz LE, Wörns MA, Galle PR, Marquardt JU.
タイトル Ginkgo biloba induces different gene expression signatures and oncogenic pathways in malignant and non-malignant cells of the liver.
ジャーナル PLoS One
Abstract Ginkgo biloba (EGb761) is a widely used botanical drug. Several reports indicate that EGb761 confers preventive as well as anti-tumorigenic properties in a variety of tumors, including hepatocellular carcinoma (HCC). We here evaluate functional effects and molecular alterations induced by EGb761 in hepatoma cells and non-malignant hepatocytes. Hepatoma cell lines, primary human HCC cells and immortalized human hepatocytes (IH) were exposed to various concentrations (0-1000 μg/ml) of EGb761. Apoptosis and proliferation were evaluated after 72h of EGb761 exposure. Response to oxidative stress, tumorigenic properties and molecular changes were further investigated. While anti-oxidant effects were detected in all cell lines, EGb761 promoted anti-proliferative and pro-apoptotic effects mainly in hepatoma cells. Consistently, EGb761 treatment caused a significant reduction in colony and sphere forming ability in hepatoma cells and no mentionable changes in IH. Transcriptomic changes involved oxidative stress response as well as key oncogenic pathways resembling Nrf2- and mTOR signaling pathway. Taken together, EGb761 induces differential effects in non-transformed and cancer cells. While treatment confers protective effects in non-malignant cells, EGb761 significantly impairs tumorigenic properties in cancer cells by affecting key oncogenic pathways. Results provide the rational for clinical testing of EGb761 in preventive and therapeutic strategies in human liver diseases.
巻・号 13(12)
ページ e0209067
公開日 2018-12-21
DOI 10.1371/journal.pone.0209067
PII PONE-D-18-02212
PMID 30576355
PMC PMC6303069
MeSH Apoptosis / drug effects Carcinogenesis / drug effects* Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology Cell Line Cell Proliferation / drug effects Ginkgo biloba / chemistry* Ginkgo biloba / metabolism Hepatocytes / cytology Hepatocytes / drug effects Hepatocytes / metabolism Humans Liver Neoplasms / metabolism Liver Neoplasms / pathology NF-E2-Related Factor 2 / metabolism Oxidative Stress / drug effects Plant Extracts / chemistry Plant Extracts / pharmacology* Signal Transduction / drug effects TOR Serine-Threonine Kinases / metabolism Transcriptome / drug effects*
IF 2.776
引用数 3
リソース情報
ヒト・動物細胞 HuH-7