The synthesis and therapeutic effect of silicon(IV) phthalocyanines for colorectal cancer cells in photodynamic therapy by altering Wnt/β-catenin and apoptotic signaling

Journal of Photochemistry and Photobiology A: Chemistry(2024)

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Abstract
Despite available treatment approaches such as surgery, chemotherapy, and radiotherapy, colorectal cancer still ranks second among all cancers in terms of mortality rate. In this work, the study aims to investigate the photodynamic therapy effects of bis[4-({8)-[3-(trimethylamino)phenoxy]octyl}oxy)] substituted (2a), ({3,5-bis[3-(4-acetylpiperazin-1-yl)propoxy]phenyl}methoxy) substituted (3a), and [3,5-bis(3-pyridinium-4-ylpropoxy)phenyl]methoxy substituted silicon (IV) phthalocyanine (4a) against colorectal cancer cells (HCT-116) and their relationship with the canonical Wingless/integrase-1 (Wnt) pathway, which is involved in the pathophysiology of colorectal cancer, in their actions. The cytotoxic/phototoxic properties and cell death mechanism were examined using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay, annexin V/FITC/propidium iodide (PI) apoptosis detection assay, and western blot analysis. The results showed that 3a had statistically significant phototoxic properties against HCT-116 cells. In addition, 3a induced apoptosis on HCT-116 cells in the presence of light irradiation. The western blot analysis showed that HCT-116 cells incubated with 3a exhibited APC and β-catenin expressions significantly decreased in the presence of light irradiation compared to the control group (p < 0.05, p < 0.001). Moreover, the caspase-3 level was significantly increased with 3a in the presence of light irradiation when compared to the control group (p < 0.05). In light of these results, 3a appeared to be a promising novel photosensitizer agent for colorectal cancer treatment.
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Key words
Apoptosis,Colorectal cancer,Photodynamic therapy,Silicon phthalocyanine,Wnt/β-catenin
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