Tumor Biology

, Volume 34, Issue 1, pp 241–249 | Cite as

Induction of apoptosis by Trichostatin A in human breast cancer cell lines: involvement of 15-Lox-1

  • Masoumeh Tavakoli-Yaraki
  • Fatemeh Karami-Tehrani
  • Vahid Salimi
  • Majid Sirati-Sabet
Research Article

Abstract

15-Lipoxygenase-1 (15-Lox-1) is a key enzyme mediating oxidative metabolism of polyunsaturated fatty acids and has attracted considerable interest as a potential target for the induction of apoptosis in cancer cells. Knowledge of relationship between 15-Lox-1 and histone deacetylase inhibitors is lacking in the breast cancer. This study is aimed to investigate the role of Trichostatin A (TSA) and 13(S)-HODE, as a metabolite of 15-Lox-1, in the regulation of breast cancer cell growth. The cytotoxic effect of TSA, as a potent HDAC inhibitor, was measured using MTT assay. Annexin V–FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The role of 15-Lox-1 in the regulation of cell growth was assessed by 15-Lox-1 inhibitor and the level of 15-Lox-1 metabolite was measured to determine 15-Lox activity after treatment by TSA. The results demonstrated that TSA induced cell growth inhibition via 15-Lox-1, in a dose- and time-dependent manner, and subsequently accompanied by the cell cycle arrest and induction of apoptosis. Moreover, growth inhibitory effect of TSA was associated with the elevation of 15-Lox-1 metabolite (13(S)-HODE). This study provided evidences that the inhibitory effect of TSA on the breast cancer cell growth occurs via the induction of 15-Lox-1 activity and 13(S)-HODE production. Our findings underline the possible role of 15-Lox-1/13(S)-HODE pathway as a promising molecular approach for the induction of apoptosis in breast cancer cells.

Keywords

15-Lipoxygenase-1 13(S)-HODE Trichostatin A Apoptosis Cell cycle arrest 

Abbreviations

15-Lox-1

15-Lipoxygenase-1

HDAC inhibitor

Histone deacetylase inhibitor

TSA

Trichostatin A

PUFA

Polyunsaturated fatty acid

13(S)-HODE

13-S-hydroxyoctadecadienoic acid

15(S)-HETE

15-S-Hydroxyeicosatetraenoic acid

HAT

Histone acetyltransferase

HDAC

Histone deacetylase

MTT

3-(4,5-Dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide

ER

Estrogen receptor

FITC

Fluorescein isothiocyanate

PI

Propidium iodide

Notes

Acknowledgement

Part of this work was supported by a PhD grant (to Masoumeh Tavakoli-Yaraki) from Tarbiat Modares University.

Conflicts of interest

The authors declare that there is no conflict of interest.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Masoumeh Tavakoli-Yaraki
    • 1
  • Fatemeh Karami-Tehrani
    • 1
  • Vahid Salimi
    • 2
  • Majid Sirati-Sabet
    • 3
  1. 1.Cancer Research Laboratory, Department of Clinical Biochemistry, School of Medical SciencesTarbiat Modares UniversityTehranIran
  2. 2.Department of Virology, School of Public HealthTehran University of Medical SciencesTehranIran
  3. 3.Department of Biochemistry and Genetic, School of MedicineQazvin University of Medical SciencesQazvinIran

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