Mareike Ströfer1, Wolfgang Jelkmann, Reinhard Depping. 1. Department of Physiology, Center for Structural and Cell Biology in Medicine, University of Luebeck, Luebeck, Germany. troefer@physio.uni-luebeck.de
Abstract
BACKGROUND: Curcumin, a commonly used spice, affects the activities of cytokines, enzymes, and transcription factors that are linked to inflammation. Furthermore, curcumin has been assigned tumor growth inhibiting effects, possibly mediated by promoting hypoxia-inducible factor (HIF) degradation. HIFs are transcription factors that play a central role in the adaptation and response to low oxygen levels in metazoan cells. However, curcumin also exhibits properties of an iron chelator indicating its potential of inhibiting HIF-α prolyl hydroxylase (PHD) activity. METHODS: We were interested in clarifying these divergent actions of curcumin in due consideration of the effects on radio-therapy. Thus, concentration- and time-dependent effects of curcumin on HIF-α and -β protein levels and activity in hepatoma and breast carcinoma cell cultures under normoxic and hypoxic conditions were studied. RESULTS: It was shown that HIF-1α accumulated in normoxia after the application of higher doses of the drug. Curcumin proved to lower HIF-1α and HIF-2α protein levels in hypoxia. HIF-1β (ARNT; arylhydrocarbon nuclear translocator) protein levels and HIF transcriptional activity were reduced in normoxia and hypoxia after 4 h and 24 h incubation periods. Furthermore, curcumin treatment negatively impacted on clonogenic cell survival of Hep3B hepatoma and MCF-7 breast carcinoma cells. CONCLUSION: Effects of curcumin on cell growth and survival factor expression suggest its potential benefit in the treatment of cancer without a direct radiosensitizing influence of curcumin on these cells.
BACKGROUND:Curcumin, a commonly used spice, affects the activities of cytokines, enzymes, and transcription factors that are linked to inflammation. Furthermore, curcumin has been assigned tumor growth inhibiting effects, possibly mediated by promoting hypoxia-inducible factor (HIF) degradation. HIFs are transcription factors that play a central role in the adaptation and response to low oxygen levels in metazoan cells. However, curcumin also exhibits properties of an iron chelator indicating its potential of inhibiting HIF-α prolyl hydroxylase (PHD) activity. METHODS: We were interested in clarifying these divergent actions of curcumin in due consideration of the effects on radio-therapy. Thus, concentration- and time-dependent effects of curcumin on HIF-α and -β protein levels and activity in hepatoma and breast carcinoma cell cultures under normoxic and hypoxic conditions were studied. RESULTS: It was shown that HIF-1α accumulated in normoxia after the application of higher doses of the drug. Curcumin proved to lower HIF-1α and HIF-2α protein levels in hypoxia. HIF-1β (ARNT; arylhydrocarbon nuclear translocator) protein levels and HIF transcriptional activity were reduced in normoxia and hypoxia after 4 h and 24 h incubation periods. Furthermore, curcumin treatment negatively impacted on clonogenic cell survival of Hep3B hepatoma and MCF-7 breast carcinoma cells. CONCLUSION: Effects of curcumin on cell growth and survival factor expression suggest its potential benefit in the treatment of cancer without a direct radiosensitizing influence of curcumin on these cells.
Authors: Mans Broekgaarden; Ruud Weijer; Thomas M van Gulik; Michael R Hamblin; Michal Heger Journal: Cancer Metastasis Rev Date: 2015-12 Impact factor: 9.264
Authors: A Yaromina; S Meyer; C Fabian; K Zaleska; U G A Sattler; L A Kunz-Schughart; W Mueller-Klieser; D Zips; M Baumann Journal: Strahlenther Onkol Date: 2012-02-16 Impact factor: 3.621