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.

Dihydroartemisinin Accentuates the Anti-Tumor Effects of Photodynamic Therapy via Inactivation of NF-κB in Eca109 and Ec9706 Esophageal Cancer Cells

“…However, PDT could induce the activation of nuclear factor-kappa B (NF-κB) [8,9,10]. Several studies have indicated that NF-κB activation plays a negative role in PDT.…”

Breast Cancer and Current Therapeutic Approaches: From Radiation to Photodynamic Therapy

“…However, the light-independent action of HY generally requires markedly higher doses. The significance of proper light regime has also been suggested by us (Kuliková et al, 2010;Sačková et al, 2005) and it is now beyond doubt that low light doses induce photo-tolerance. Discontinuity time proved to be crucial.…”

“…The main advantage of this approach is the combination of three inoffensive entities which together create a highly toxic conjunction, and so it has also found applications in the treatment of a wide range of malignancies (Ledo & Ledo, 2000). By its nature, PDT is a flexible and versatile therapeutic approach depending on the nature of the photosensitive compound, its concentration and incubation time, on the wavelength of light radiation, fluence rate and light dose, the time between drug administration and its activation (Kuliková et al, 2010), as well as on the histological origin of tissue and the oxygen pressure in it (Agostinis et al, 2002). All these factors modulate three independent processes contributing to tumour destruction by PDT: direct cell death, destruction of tumour vasculature causing tumour ischemia, and activation of an immune response (Buytaert et al, 2007).…”

Resistência de células de carcinoma epidermóide bucal à terapia fotodinâmica mediada pelo ácido 5-aminolevulínico

“…O aumento da expressão de NFB em células sobreviventes tratadas com PDT já foi descrito em outros estudos com outras linhagens celulares e protocolos diversos de tratamento (Matroule et al, 2001;Kuliková et al, 2010). Em geral os autores concluem que o NFB desempenha um papel de proteção contra a apoptose induzida pela PDT, sendo responsável por vários mecanismos de resistência a essa terapia.…”

“…Os estudos demonstram ativação de vias celulares relacionadas à sobrevivência celular, ou seja, que promovem evasão da apoptose e proliferação celular. Por exemplo, menção tem sido feita à superexpressão de Akt (Song et al, 2013), NFB (Kuliková et al, 2010), iNOS Girotti, 2013) e proteína anti-apoptótica Bcl-2 (Shen et al, 2005) Não há relatos na literatura do desenvolvimento de células de CEC bucal resistentes a PDT, nem tampouco quando a PDT é mediada pelo ácido 5-aminolevulínico (5-ALA) nesses tumores. Esse FS tem sido utilizado para casos de lesões potencialmente malignais na cavidade bucal (Chen et al, 2005;Tsai et al, 2004), bem como para carcinomas verrucosos e CEC pouco invasivos Fan et al, 1996).…”