Photodynamic activity of Zn(II) phthalocyanines containing polyoxyethylene side chains in malignant melanoma and colorectal cancer cell lines

Photodynamic therapy (PDT) is a treatment modality that activates apoptosis as the preferred pathway of cell death by exposing the target area to light of a wavelength within the spectrum of an administered photosensitizer (PS). Here, we aimed to investigate the anticancer mechanisms of non-peripheral zinc phthalocyanines substituted with either four (np-O-ZnPc1 and np-S-ZnPc1) or eight (np-O-ZnPc2 and np-S-ZnPc2) triethylene monomethyl glycol groups to compare the effects of heteroatoms and substituent number in a systematic manner. Comparison with unsubstituted Zn(II)-phthalocyanine (ZnPc) suggests that substitution of triethylene monomethylglycol with ZnPc tends to increase the singlet oxygen yield while decreasing the fluorescence quantum yield for all compounds. In addition, an increasing fluorescence half-life was observed with the exception of np-O-ZnPc2. The cytotoxicity of the compounds was evaluated on colorectal cancer (HCT116), malignant melanoma (SH-4) and a skin keratinocyte cell line (HaCaT). The optimal incubation time and light dose were determined and the half maximal inhibitory concentrations (IC50) for each cell line were calculated. Programmed cell death pathways, mitochondrial function and protein expression of chemokine receptors were examined. The compounds significantly reduced cell viability and promoted apoptosis in both cancer cell lines. Structurally, compounds with oxygen heteroatoms exhibited higher anticancer activity than those with sulfur atoms. The observation of an increase in CCR7 and CXCR4 proteins as a result of PDT highlights the need for further detailed evaluation of the effects of PDT with the offered phthalocyanines on the invasive and migratory properties of cancer cells.