Curcumin decreases survival of Hep3B liver and MCF-7 breast cancer cells: The role of HIF

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 pro-moting 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-1ß (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.