Strahlentherapie und Onkologie

, Volume 187, Issue 7, pp 393–400

Curcumin Decreases Survival of Hep3B Liver and MCF-7 Breast Cancer Cells

The Role of HIF
  • Mareike Ströfer
  • Wolfgang Jelkmann
  • Reinhard Depping
Original Article

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.

Key Words

Curcumin HIF ARNT Radiosensitivity Apoptosis Cancer 

Curcumin senkt die Überlebensrate von Hep3B-Leber- und MCF-7-Brusttumorzellen – die Rolle von HIF

Hintergrund:

Das traditionell verwendete Gewürz Kurkumin beeinflusst die Aktivität von Entzündungsvermittlern wie Zytokinen und Transkriptionsfaktoren. Weiterhin hat Kurkumin inhibierenden Einfluss auf das Tumorwachstum – möglicherweise hervorgerufen durch einen verstärkten Abbau des Hypoxie-induzierbaren Faktors (HIF). Dieser Transkriptionsfaktor spielt eine entscheidende Rolle bei der Anpassung an eine verminderte Sauerstoffverfügbarkeit im Organismus. Dem entgegen könnte Kurkumin aber auch – aufgrund seiner Struktur – Eisen-Ionen komplexieren und so die Aktivität HIF-inhibierender Prolylhydroxylasen (PHD) beeinflussen. Gegenstand dieser Untersuchungen war daher die Klärung dieser divergenten Mechanismen in Bezug auf die Bestrahlungseffizienz von Tumoren.

Methoden:

Hierfür wurden die Poteinmengen der HIF-Untereinheiten sowie die HIF-Aktivität nach Kurkumin-Behandlung von Leber- und Brusttumorzellen innerhalb festgelegter Zeit- und Konzentrationsfenster geprüft. Anschließend wurde der Einfluss von Kurkumin auf die Strahlensibilität der Zellen im Klonogenen Assay untersucht.

Ergebnisse:

Es zeigte sich eine konzentrationsabhängige leichte Stabilisierung von HIF-1α-Protein unter normoxischen sowie eine Abnahme von HIF-1α-, -2α- und -1β-(ARNT: Arylhydrocarbon Nuclear Translocator-)Proteinmengen unter hypoxischen Bedingungen nach 4 Stunden Kurkumin-Behandlung. Die Aktivität von HIF nahm ebenfalls konzentrationsabhängig nach 4 h und 24 h Kurkumin-Inkubation ab. Weiterhin hatte die Vorbehandlung mit Kurkumin einen negativen Einfluss auf das klonogene Wachstum der untersuchten Leber- und Brusttumorzellen.

Schlussfolgerung:

Die Untersuchungen zur Kurkumin-Wirkung auf Tumorzellen sind ein Indiz für einen potentiell positiven Einfluss von Kurkumin auf den Bestrahlungserfolg dieser Zellen.

Schlüsselwörter

Kurkumin HIF ARNT Bestrahlungssensitivität Apoptose Krebs 

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Copyright information

© Urban & Vogel 2011

Authors and Affiliations

  • Mareike Ströfer
    • 1
    • 2
    • 3
  • Wolfgang Jelkmann
    • 1
  • Reinhard Depping
    • 1
  1. 1.Department of Physiology, Center for Structural and Cell Biology in MedicineUniversity of LuebeckLuebeckGermany
  2. 2.Department of RadiotherapyCampus LuebeckLuebeckGermany
  3. 3.Institute of PhysiologyUniversity of LübeckLübeckGermany

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