NF-κB is Not Directly Responsible for Photoresistance Induced by Fractionated Light Delivery in HT-29 Colon Adenocarcinoma Cells

Authors

  • Lucia Kuliková,

    1. Faculty of Sciences, Institute of Biology and Ecology, P.J. Šafárik University, Košice, Slovakia
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    • The contributions of these authors are considered equal.

  • Jaromír Mikeš,

    1. Faculty of Sciences, Institute of Biology and Ecology, P.J. Šafárik University, Košice, Slovakia
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    • The contributions of these authors are considered equal.

  • Martina Hýžďalová,

    1. Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic
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  • Giuseppe Palumbo,

    1. Dipartmento di Biologia e Patologia Cellulare e Molecolare “L. Califano,” Università di Napoli “FEDERICO II,” Naples, Italy
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  • Peter Fedoročko

    Corresponding author
    1. Faculty of Sciences, Institute of Biology and Ecology, P.J. Šafárik University, Košice, Slovakia
      Corresponding author email: peter.fedorocko@upjs.sk (Peter Fedoročko)
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Corresponding author email: peter.fedorocko@upjs.sk (Peter Fedoročko)

Abstract

Our recent study follows up an earlier one which demonstrated hypericin-mediated photocytotoxic effects on HT-29 adenocarcinoma cells by light fractionation with a longer dark pause between two unequal light doses (Sackova, A. [2005] Photochem. Photobiol.81, 1411–1416). Here, we present closer study on events invoked by sublethal light dose (1 J cm−2) during the period of 6 h that is sufficient to invoke resistance to second lethal dose (11 J cm−2). First, we proved that the dark pause of 6 h, but not 1 h, resulted in better cell survival with suppressed phosphatidylserine externalization, decreased reactive oxygen species production and hypericin content as well as altered expression of HSP70, GRP94, clusterin, nuclear factor (NF)-κB, IκB-α or Mcl-1. NF-κB activity assay confirmed activation of this early-response pathway. However, inhibition of IκB (IKK) kinase by parthenolide by stopping NF-κB release from the complex with IκB did not prevent onset of resistance, but it invoked some resistance even in groups with shorter, 1 h dark pause. Therefore, we predict involvement of another signaling pathway, located upstream from NF-κB, responsible for onset of resistance to photodynamic therapy with hypericin in colon adenocarcinoma cells HT-29.

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