NF-κB is not directly responsible for photoresistance induced by fractionated light delivery in HT-29 colon adenocarcinoma cells.

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.

journal_name

Photochem Photobiol

authors

Kuliková L,Mikeš J,Hýžďalová M,Palumbo G,Fedoročko P

doi

10.1111/j.1751-1097.2010.00788.x

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1285-93

issue

6

eissn

0031-8655

issn

1751-1097

pii

PHP788

journal_volume

86

pub_type

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