Characterization of resistant MCF-7 breast cancer cells developed by repeated cycles of photodynamic therapy

Abstract

Breast cancer mainly affects women and causes a severe global threat to health. It is often managed and treated with surgery, chemotherapy, immunotherapy, and radiation therapy. Generally, chemotherapy as a treatment option is often opposed by responsive tumor relapse and development of resistance, a significant setback of current treatment. Photodynamic therapy (PDT) offers a promising modality that can treat cancer by combining a photosensitizer and laser irradiation in the presence of oxygen. However, one problem of PDT in treating breast cancer is the apparition of the resistant cell population. Thus, we aimed for stepwise selection and characterization of MCF-7 cells resistant to PDT with a sulfonated zinc phthalocyanine (ZnPcS4) photosensitizer. The wild-type MCF-7 was exposed to successive cycles of ZnPcS4-PDT, and 10resistant populations were finally obtained. In wild-type and parental cells, we analyzed the cell morphology (light microscopy), cell cycle (BrdU staining), cell viability (MTT assay), antioxidant activity (superoxide dismutase measurement), and immunofluorescence expression of resistant p-glycoprotein (P-gp). The results indicate that resistant cells showed a mesenchymal cell phenotype, few differences in antioxidant activity, an increased DNA synthesis, and more expression of P-gp than the wild-type parental cells. These distinctive features of resistant cells can provide insight into the emergence of MCF-7 cell resistance to PDT, which was necessary to design the best therapeutic procedure for improved efficacy.

Cyanocobalamin (vitamin B12) as insensitive porphyrinoid to solar LED irradiation

“…However, the photoactive compounds have phototoxic effect not only after irradiation with a spectrum overlapping their absorption, but also for appropriate characteristics of the light source such as the power and continuous or pulse light. The mechanism of the phototoxic effect mediated by porphyrinoids is mainly based on the production of singlet oxygen and in a lower extent -on other reactive oxygen [15]. The phenomenon photodynamic action includes synchronised action of a photosensitizer (PS), molecular oxygen from the environment and exposure to light with appropriate wavelength, which is followed by the production of highly reactive oxygen species (ROS), and finally the irreversible oxidation of cellular components can happen [16].…”

“…The electronic configuration of molecular oxygen such as its outer shell with two unpaired electrons having parallel spins obviously leads to a spin restriction. The one-electron redox reactions can occur with other atoms or molecules, which results in several highly-reactive short-living species, such as superoxide anion (O2 •− ), hydroxyl radical and finally to the stable hydrogen peroxide [15,16]. The free radicals can lose electrons reacting with the surrounding biomolecules, which after oxidation produce radicals and the chain cascade reaction continues with destructive action on the cells.…”