Abstract
Photodynamic therapy (PDT) is a cancer treatment modality that utilizes three components: light (λ 650–750 nm), a photosensitizer (PS) and molecular oxygen, which upon activation renders the modality effective. Colorectal cancer has one of the highest incident rates as well as a high mortality rate worldwide. In this study, a zinc (Zn) metal-based phthalocyanine (ZnPcSmix) PS was used to determine its efficacy for the treatment of colon adenocarcinoma cells (DLD-1 and Caco-2). Photoactivation of the PS was achieved by laser irradiation at a wavelength of 680 nm. Dose responses were performed to establish optimal PS concentration and irradiation fluence. A working combination of 20 µM ZnPcSmix and 5 J/cm2 was used. Biochemical responses were determined after 1 or 24 h incubation post-treatment. Since ZnPcSmix is localized in lysosomes and mitochondria, mitochondrial destabilization analysis was performed monitoring mitochondrial membrane potential (MMP). Cytosolic acidification was determined measuring hydrogen peroxide (H2O2) levels in the cytoplasm. Having established apoptotic cell death induction, an apoptosis PCR array was performed to establish the apoptotic mechanism. In DLD-1 cells, expression of genes included 3 up-regulated and 20 down-regulated genes while in Caco-2 cells, there were 16 up-regulated and 22 down-regulated genes. In both cell lines, in up-regulated genes, there was a combination of pro- and anti-apoptotic genes that were significantly expressed. Gene expression results showed that more tumorigenic cells (DLD-1) went through apoptosis; however, they exhibit increased risk of resistance and recurrence, while less tumorigenic Caco-2 cells responded better to PDT, thus being suggestive of a better prognosis post-PDT treatment. In addition, the possible apoptotic mechanisms of cell death were deduced based on the genetic expression profiling of regulatory apoptotic inducing factors.
Highlights
Colorectal cancer is highly metastatic due to amplified migration, proliferation and adhesion rate
After 1 h incubation, irradiated (5 J/cm2) and ZnPcSmix treated DLD-1 cells showed no significant difference in H2O2 levels in comparison to untreated control cells (Figure 1)
After 24 h incubation, DLD-1 cells treated with ZnPcSmix alone as well as Photodynamic therapy (PDT) treated cells showed a significant increase in H2O2 levels compared to the untreated control cells (p < 0.05 and p < 0.001, respectively)
Summary
Colorectal cancer is highly metastatic due to amplified migration, proliferation and adhesion rate. The disease is difficult to treat due to the prevalent recurrence rate. Cancer progresses as a result of the cells’ failure to undergo genetically regulated apoptosis. The apoptotic cell death pathway is a preferred mode of cell death as it plays an important role in the regulation of homeostasis. Radiotherapy, surgical removal or a combination of the latter treatments for the disease yields successful removal of the tumor mass, but does not improve patient morbidity and survival or reduce the recurrence rate. The success of the latter treatments is limited by the progression stage of the cancer [1]
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