NF-κB is not directly responsible for photoresistance induced by fractionated light delivery in HT-29 colon adenocarcinoma cells.
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.
Kuliková
Lucia
L
Faculty of Sciences, Institute of Biology and Ecology, P.J. Šafárik University, Košice, Slovakia.
Mikeš
Jaromír
J
Hýžďalová
Martina
M
Palumbo
Giuseppe
G
Fedoročko
Peter
P
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000873:Anthracenes; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D019073:HT29 Cells; D006801:Humans; D008027:Light; D016328:NF-kappa B / Q000378:metabolism*; D010569:Perylene / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D010778:Photochemotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014410:Tumor Stem Cell Assay
D000873:Anthracenes; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D010569:Perylene; C004965:hypericin