Synthesis and characterization of novel Schiff base-silicon (IV) phthalocyanine complex for photodynamic therapy of breast cancer cell lines.

BACKGROUND: Photodynamic therapy is an alternative anticancer treatment approach that promises high therapeutic efficacy. In this study, it is aimed to investigate the PDT-mediated anticancer effects of newly synthesized silicon phthalocyanine (SiPc) molecules on MDA-MB-231, MCF-7 breast cancer cell lines, and non-tumorigenic MCF-10A breast cell line. METHODS: Novel bromo substituted Schiff base (3a), its nitro homolog (3b), and their silicon complexes (SiPc-5a and SiPc-5b) were synthesized. Their proposed structures were confirmed by FT-IR, NMR, UV-vis and MS instrumental techniques. MDA-MB-231, MCF-7 and MCF-10A cells were illuminated at a light wavelength of 680 nm for 10 min, giving a total irradiation dose of 10 j/cm2. MTT assay was used to determine the cytotoxic effects of SiPc-5a and SiPc-5b. Apoptotic cell death was analyzed using flow cytometry. Changes in the mitochondrial membrane potential were determined by TMRE staining. Intracellular ROS generation was observed microscopically using H2DCFDA dye. Colony formation assay and in vitro scratch assay were performed to analyze the clonogenic activity and cell motility. Transwell migration and matrigel invasion analyzes were conducted to observe changes in the migration and invasion status of the cells. RESULTS: The combination of SiPc-5a and SiPc-5b with PDT exhibited cytotoxic effects on cancer cells and triggered cell death. SiPc-5a/PDT and SiPc-5b/PDT decreased mitochondrial membrane potential and increased intracellular ROS production. Statistically significant changes were detected in cancer cells' colony-forming ability and motility. SiPc-5a/PDT and SiPc-5b/PDT reduced cancer cells' migration and invasion capacities. CONCLUSION: The present study identifies PDT-mediated antiproliferative, apoptotic, and anti-migratory characteristics of novel SiPc molecules. The outcomes of this study emphasize the anticancer properties of these molecules and suggest that they may be evaluated as drug-candidate molecules for therapeutic purposes.

Novel piperazine-substituted silicon phthalocyanines exert anti-cancer effects against breast cancer cells.

BACKGROUND: Photodynamic therapy (PDT) is one of the effective methods that can be used in cancer treatment. In this study, we aimed to investigate the PDT-mediated anti-cancer effects of newly synthesized piperazine-substituted silicon phthalocyanine molecules on breast cancer cells. METHODS: The compounds were analyzed by different spectroscopic techniques (FT-IR, UV-vis, 1H NMR, 13C NMR, MS) and the absorbance characteristics were determined. The cytotoxic effects of silicon phthalocyanines on MDA-MB-231 breast cancer cells and non-tumorigenic MCF-10A cells were evaluated using MTT assay. Detection of apoptotic populations was performed by Annexin V/7AAD assay. H2DCFDA dye was used to analyze intracellular reactive oxygen species. The clonogenic activity and cellular motility were analyzed by colony formation assay and in vitro scratch assay, respectively. Caspase-3, PARP1, and cleaved-PARP1 protein levels were analyzed by western blot studies. RESULTS: Piperazine-substituted silicon phthalocyanines caused high levels of cytotoxic effects and apoptotic cell population in MDA-MB-231 cells, while low levels of cytotoxic effects were observed in MCF-10A cells. Following PDT, intense ROS formation was detected in MDA-MB-231 cells. Colony-forming capacity and cellular motility of MDA-MB-231 cells were highly restricted following PDT, whereas these effects were observed at lower levels in MCF-10A cells. Silicon phthalocyanines caused different effects on cleaved-PARP1 expressions of MDA-MB-231 and MCF-10A cells. CONCLUSION: These results suggest that piperazine-substituted silicon phthalocyanines can exert selective anti-cancer effects on breast cancer cells and activate cellular death through different molecular pathways. Hence, we believe that they may be used as effective photosensitizer agents in the future.

Synthesis and photodynamic efficacy of water-soluble protoporphyrin IX homologue with mPEG550.

Protoporphyrin IX (PpIX), which is an efficient photosensitive agent, cannot be used directly in photodynamic therapy due to its aggregation in physiological environment. If PpIX is made water-soluble without losing its photosensitive properties, it can be used in many medical fields, including cancer treatment. Here we report synthesis of PpIX homologue with mPEG550 (Porfipeg) and its photodynamic effects on both in-vitro and in-vivo environment. Porfipeg is synthesized to give PpIX the ability to dissolve in water. Spectrometric (FT-IR, NMR, MS, UV-vis and Fluorescence) measurements were performed. Porfipeg can penetrate into the cells and indicates no cytotoxicity in the dark whereas cell viability significantly reduced with light irradiation. The cells can be visualized by fluorescence microscope. In-vivo experiment revealed that intravenous injection of Porfipeg is more efficient than intraperitoneal injection for the acute photodynamic effects within 30 min. Moreover it is excreted by the kidneys. In conclusion, Porfipeg has remarkable potentials to be used in both fluorescence guidance in surgeries and photodynamic therapy for cancer treatment.

Synthesis of axially disubstituted silicon phthalocyanines and investigation of photodynamic effects on HCT-116 colorectal cancer cell line.

Photodynamic therapy is one of the hot topics in cancer studies. Photosensitizing chemical substrates are stimulated by light having a specific wavelength to cause fatal effect on different kinds of targets. In this study, axially 4-{[(1E)-2-furylmethylene]amino}phenol, 4-{[(1E)-2-thienylmethylene]amino}phenol and 4-{[(1E)-(4-nitro-2-thienyl)methylene]amino}phenol disubstituted silicon phthalocyanines were synthesized as Photosensitizers for photodynamic therapy in cancer treatment. The structural characterizations of these novel compounds were performed by a combination of FT-IR, 1H-NMR, UV-vis and mass. All these newly prepared compounds did not show aggregation at the concentration range of 2 × 10-6-12 × 10-6 M in tetrahydrofurane and also did not show aggregation in different organic solvents at 2 × 10-6 M concentration. Phthalocyanines synthesized in this study were tested on HCT-116 colorectal cancer cells and stimulated by light has wavelength of 680 nm. The toxic effects on cancer cells which are caused by different concentrations of photosensitizing molecules have been examined and compared with the toxic effects on cancer cells that were kept in the dark. It is confirmed that these molecules caused toxic effects on colorectal cancer cells when they were stimulated by light but there was no toxic effect in the dark.