5E, 8Z, HZ, 14Z-eicosatetraenoic acid, a novel transisomer of arachidonic acid, causes G1 phase arrest and induces apoptosis of HL-60 cells

Kavita Jain, Uzzal Roy, Barbara Ardelt, U. M. Krishna, J R Falck, Piotr Pozarowski, Jan Kunicki, Zbigniew Darzynkiewicz, Michael Balazy

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Trans arachidonic acid isomers (trans-AA) constitute a new group of trans fatty acids (trans-FA) generated in vivo via endogenous cis-trans isomerization stimulated by the NO2 radical. Because both NO2 and trans-FA have been implicated as causative factors in cancer, we studied the effect of the trans-AA isomers on proliferation and viability of human promyelocytic (HL-60) cells. The four trans arachidonic (trans-AA) acid isomers synthesized by us have been presently tested with respect to their competence to affect the proliferation and viability of humal promyeolocytic HL-60 cells in culture. The data demonstrate that one of the isomers, 5,6-trans-AA, showed distinct activity by targeting cell progression through the cell cycle and inducing apoptosis. The effects were time- and concentration-dependent: the cytostatic effect of 5E-AA was observed at 10 μM following 72 h of treatment. This effect was manifested as a perturbation of cell progression through G 1, phase, indicating the ′on′ activation of the G 1, checkpoint as evidenced by the flow- and laser scanning-cytometry techniques. Apoptotic cells were identified by comparison of their morphology, DNA fragmentation, caspase activation and collapse of mitochondrial potential with control cells. These observations suggested that 5E-AA induced a mitochondrial pathway of apoptosis. There was no evidence of cell-cycle phase specificity in induction of apoptosis by 5E-AA, as the cells showing highly fragmented DNA or caspase-3 activation were distributed in all phases of the cycle. The data suggest that 5E-AA may have at least two targets: one that is cell-cycle specific and associated with the observed arrest in the G1 phase and another, unrelated to the cell cycle, which is responsible for triggering apoptosis indiscriminately, regardless of cycle phase I.

Original languageEnglish (US)
Pages (from-to)1177-1185
Number of pages9
JournalInternational journal of oncology
Volume27
Issue number5
StatePublished - Nov 1 2005

Keywords

  • Apoptosis
  • Arachidonic acid
  • Eicosatetraenoic acid
  • HL-60 cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Jain, K., Roy, U., Ardelt, B., Krishna, U. M., Falck, J. R., Pozarowski, P., Kunicki, J., Darzynkiewicz, Z., & Balazy, M. (2005). 5E, 8Z, HZ, 14Z-eicosatetraenoic acid, a novel transisomer of arachidonic acid, causes G1 phase arrest and induces apoptosis of HL-60 cells. International journal of oncology, 27(5), 1177-1185.