The Journal of nutritional biochemistry, 2017-03, Vol.41, p.124-136
2017
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- Autor(en) / Beteiligte
- Titel
- Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways
- Ist Teil von
- The Journal of nutritional biochemistry, 2017-03, Vol.41, p.124-136
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Quercetin, a bioflavonoid contained in several vegetables daily consumed, has been studied for long time for its antiinflammatory and anticancer properties. Quercetin interacts with multiple cancer-related pathways such as PI3K/AKT, Wnt/β-catenin and STAT3. These pathways are hyperactivated in primary effusion lymphoma (PEL), an aggressive B cell lymphoma whose pathogenesis is strictly linked to the oncogenic virus Kaposis' Sarcoma-associated Herpesvirus (KSHV). In this study, we found that quercetin inhibited PI3K/AKT/mTOR and STAT3 pathways in PEL cells, and as a consequence, it down-regulated the expression of the prosurvival cellular proteins such as c-FLIP, cyclin D1 and cMyc. It also reduced the release of IL-6 and IL-10 cytokines, leading to PEL cell death. Moreover, quercetin induced a prosurvival autophagy in these cells and increased the cytotoxic effect of bortezomib, a proteasomal inhibitor, against them. Interestingly, quercetin decreased also the expression of latent and lytic KSHV proteins involved in PEL tumorigenesis and up-regulated the surface expression of HLA-DR and calreticulin, rendering the dying cells more likely detectable by the immune system. The results obtained in this study indicate that quercetin, which does not exert any cytotoxicity against normal B cells, may represent a good candidate for the treatment of this aggressive B cell lymphoma, especially in combination with autophagy inhibitors or with bortezomib. [Display omitted]
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0955-2863eISSN: 1873-4847DOI: 10.1016/j.jnutbio.2016.12.011Titel-ID: cdi_proquest_miscellaneous_1861539415
- Format
- –
- Schlagworte
- Antineoplastic Agents - chemistry, Antineoplastic Agents - pharmacology, Antineoplastic Agents, Phytogenic - adverse effects, Antineoplastic Agents, Phytogenic - metabolism, Apoptosis - drug effects, Autophagy - drug effects, B-Lymphocytes - cytology, B-Lymphocytes - drug effects, B-Lymphocytes - immunology, B-Lymphocytes - metabolism, Bortezomib - agonists, Bortezomib - pharmacology, Cell Line, Tumor, Cells, Cultured, Down-Regulation - drug effects, Drug Agonism, Humans, Il-6, Interleukins - antagonists & inhibitors, Interleukins - metabolism, KSHV, Lymphoma, Primary Effusion - drug therapy, Lymphoma, Primary Effusion - immunology, Lymphoma, Primary Effusion - metabolism, Lymphoma, Primary Effusion - pathology, mTOR/PI3K/AKT, Neoplasm Proteins - antagonists & inhibitors, Neoplasm Proteins - metabolism, PEL, Phosphatidylinositol 3-Kinase - antagonists & inhibitors, Phosphatidylinositol 3-Kinase - metabolism, Proteasome Inhibitors - chemistry, Proteasome Inhibitors - pharmacology, Proto-Oncogene Proteins c-akt - antagonists & inhibitors, Proto-Oncogene Proteins c-akt - metabolism, Quercetin, Quercetin - adverse effects, Quercetin - metabolism, Recombinant Fusion Proteins - chemistry, Recombinant Fusion Proteins - genetics, Recombinant Fusion Proteins - metabolism, Signal Transduction - drug effects, STAT3, STAT3 Transcription Factor - antagonists & inhibitors, STAT3 Transcription Factor - metabolism, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - metabolism