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Molecular and Cellular Biochemistry

, Volume 383, Issue 1–2, pp 243–251 | Cite as

Pronounced transcriptional regulation of apoptotic and TNF–NF-kappa-B signaling genes during the course of thymoquinone mediated apoptosis in HeLa cells

  • Cagri SakalarEmail author
  • Merve Yuruk
  • Tugba Kaya
  • Metin Aytekin
  • Salih Kuk
  • Halit Canatan
Article

Abstract

Thymoquinone (TQ) is the active ingredient extracted from the essential oil of Nigella sativa. A number of studies implicated TQ as an antitumor agent. In this study, cytotoxic effects of the oil of N. sativa and TQ were evaluated on human cervical cancer cell line, HeLa cells. IC50 value was ~0.125 μl/ml for N. sativa oil preparations and 12.5 μM for TQ. TQ strongly inhibited wound healing at all concentrations ranging from 12.5 to 100 μM in a scratch wound healing assay. Additionally, induction of apoptosis by TQ was assessed by Giemsa staining and TQ was found to induce apoptosis in cancer cells especially at concentrations of 50 and 100 μM. TQ-mediated transcriptional regulation of 84 genes involved in apoptosis was studied using a PCR array. At low dose (12.5 μM), TQ was found to induce expression of four pro-apoptotic genes: BIK (~22.7-fold), FASL (~2.9-fold), BCL2L10 (~2.1-fold), and CASP1 (~2-fold). TQ was also found to reduce the expression of an anti-apoptotic gene implicated in NF-kappa-B signaling and cancer: RELA (~8-fold). At high dose (100 μM), TQ mediated the expression of 21 genes implicated directly in apoptosis (6 genes), TNF signaling (10 genes), and NF-kappa-B signaling (3 genes) such as BIK, BID, TNFRSF10A, TNFRSF10B, TNF, TRAF3, RELA, and RELB. In conclusion, this study implicates the role of TQ in the inhibition of cancer cell proliferation and migration. At the same time, our results strongly suggest that TQ intervenes with TNF and NF-kappa-B signaling during TQ-mediated induction of apoptosis in cancer cells.

Keywords

Thymoquinone Cancer Apoptosis TNF signaling NF-kappa-B signaling 

Notes

Acknowledgments

We thank Dr. Nazmiye Bitgen for her technical support in Giemsa staining of cancer cells and assessment of apoptotic cells. This work was supported by Erciyes University Scientific Research Fund (EU-BAP), Grant Number: CAP-12-4044 (C. SAKALAR).

Conflict of Interest

All of the authors declare that they have no conflict of interest and no financial relationship with any commercial entity that has an interest in the subject of this manuscript.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Cagri Sakalar
    • 1
    • 2
    Email author
  • Merve Yuruk
    • 3
  • Tugba Kaya
    • 3
  • Metin Aytekin
    • 1
    • 2
  • Salih Kuk
    • 2
    • 3
  • Halit Canatan
    • 1
    • 2
  1. 1.Department of Medical Biology, Faculty of MedicineErciyes UniversityKayseriTurkey
  2. 2.Genome and Stem Cell Research CenterErciyes UniversityKayseriTurkey
  3. 3.Department of Parasitology, Faculty of MedicineErciyes UniversityKayseriTurkey

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