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

• Published in: Photochemistry and photobiology Vol. 86; no. 6; pp. 1285 - 1293
• Main Authors: Kuliková, Lucia, Mikeš, Jaromír, Hýžďalová, Martina, Palumbo, Giuseppe, Fedoročko, Peter
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2010
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Cell Survival - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Drug Resistance, Neoplasm; HT29 Cells; Humans; Light; NF-kappa B - metabolism; Perylene - analogs & derivatives; Perylene - metabolism; Perylene - pharmacology; Photochemotherapy; Reactive Oxygen Species - metabolism; Signal Transduction; Tumor Stem Cell Assay
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/j.1751-1097.2010.00788.x

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.