Relationship between subcellular localisation of Foscan® and caspase activation in photosensitised MCF-7 cells

Abstract

The present study investigates the relationship between the subcellular localisation of Foscan s and intrinsic apoptotic pathway post Foscan s -based photodynamic therapy (PDT). With this purpose, mammary carcinoma MCF-7 cells were incubated with Foscan s for 3 or 24 h and then subjected to equitoxic light doses. Fluorescence microscopy revealed very good Foscan s co-localization to endoplasmic reticulum (ER) and Golgi apparatus after 3 h incubation with MCF-7 cells. Progressive increase in incubation time shows leakage of Foscan s from Golgi apparatus. Twenty-four hours incubation yielded a fluence-dependent enhanced induction of the ERresident glucose-regulated protein 78 (Bip/GRP78), along with a weak mitochondrial damage, thus underscoring the ER as the main site of photodamage after prolonged incubation. Analysis of events implicated in apoptotic pathway after 24 h incubation demonstrated photodamage to Bcl-2 protein in total cellular extract, but not in the mitochondrial fraction. We further determined an increase in caspases-7 and -6 activation, which was strongly related to the expression of GRP78. The above findings demonstrate that Foscan s localisation in ER improves the photoactivation of the caspase-7 apoptotic pathway, which is poorly related to mitochondrial damage.

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

“…It had been reported that apoptotic pathways may be initiated [9][10][11][12], however, autophagy or necrosis [13] may prevail -especially if high PDT doses are applied [14].…”

Development of a multifunctional luciferase reporters system for assessing endoplasmic reticulum-targeting photosensitive compounds

“…For these reason, we applied them to verify the sensitivity and reliability of our luciferase reporter. Marchal et al (2007) proved a predominant accumulation of Foscan® in the ER after 24 h incubation. The reporter cells were treated by PDT under a specific light fluency (7.2 J/cm 2 ) with various positive compounds concentration (Me, 0∼10 μM; Foscan®, 0∼12 μM) after 24 h incubation.…”

“…It is widely reported that human breast cancer cell line MCF-7 is sensitive to ER-targeting PDT (Marchal et al 2007;Li et al 2010;Xue et al 2001). So this study applied MCF-7 as model cell.…”

Photodynamic activity of a glucoconjugated silicon(IV) phthalocyanine on human colon adenocarcinoma

“…29 When such a mechanism does not remedy the excessive oxidative stress, the "unfolded protein response" will activate the caspase cascade, resulting in apoptosis. 30 While numerous in vitro studies have been done to characterize the photodynamic activities of different photosensitizers, relatively little is known about their efficacy in the animal model.…”