NF-[kappa]B 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; p. 1285
• Main Authors: Kuliková, Lucia, Mikes, Jaromír, Hyzdalová, Martina, Palumbo, Giuseppe, Fedorocko, Peter
• Format: Journal Article
• Language: English
• Published: Lawrence Blackwell Publishing Ltd 01.11.2010
• Subjects: Apoptosis; Colorectal cancer; Oxidative stress; Photodynamic therapy; Proteins; Studies
• ISSN: 0031-8655; 1751-1097

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^sup -2^) during the period of 6 h that is sufficient to invoke resistance to second lethal dose (11 J cm^sup -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 sonic 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. [PUBLICATION ABSTRACT]