Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent colorectal cancer cells

Wirries,André; Breyer,Sandra; Quint,Karl; Schobert,Rainer; Ocker,Matthias

doi:10.3892/etm_00000058

Thymoquinone hydrazone derivatives cause cell cycle arrest in p53-competent colorectal cancer cells

Authors:
- André Wirries
- Sandra Breyer
- Karl Quint
- Rainer Schobert
- Matthias Ocker
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Affiliations: Department of Medicine 1, University Hospital Erlangen, 91054 Erlangen, Germany
Published online on: March 1, 2010 https://doi.org/10.3892/etm_00000058
Pages: 369-375

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Abstract

Thymoquinone (TQ), the major compound of black seed oil, has been shown to induce pro-apoptotic signaling pathways in various human cancer models. Although TQ is commonly used in traditional medicine, its use in humans is limited due to its chemical properties and poor membrane penetration capacity. We therefore attached saturated and unsaturated fatty acid residues to TQ and evaluated the effect on cell proliferation, apoptosis and underlying signaling pathways in HCT116 and HCT116p53−/− colon cancer and HepG2 hepatoma cells in vitro. Treatment with thymoquinone-4-α-linolenoylhydrazone (TQ-H-10) or thymoquinone-4-palmitoylhydrazone (TQ-H-11) induced a cytostatic effect, particularly in p53-competent HCT116 cells, mediated by an up-regulation of p21cip1/waf1 and a down-regulation of cyclin E, and associated with an S/G2 arrest of the cell cycle. Cells lacking p53 (HCT116p53−/−) or HepG2 liver cancer cells showed only a minor response to TQ-H-10. These findings demonstrate that derivatives of TQ inhibit cell proliferation dependent on p53 status by activating the cell cycle inhibitor p21cip1/waf1 at lower concentrations than unmodified TQ. Structural modifications can therefore contribute to the further clinical development of TQ.

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