BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and β1 integrin expression in ovarian cancer cells

Abstract

Summary Benzoporphyrin derivative monoacid (BPD-MA) photosensitization was examined for its effects on cellular adhesion of a human ovarian cancer cell line, OVCAR 3, to extracellular matrix (ECM) components. Mild BPD-MA photosensitization (~ 85% cell survival) of OVCAR 3 transiently decreased adhesion to collagen IV, fibronectin, laminin and vitronectin to a greater extent than could be attributed to cell death. The loss in adhesiveness was accompanied by a loss of β 1 integrin-containing focal adhesion plaques (FAPs), although β 1 subunits were still recognized by monoclonal antibody directed against human β 1 subunits. In vivo BPD-MA photosensitization decreased OVCAR 3 adhesiveness as well. Photosensitized adhesion was reduced in the presence of sodium azide and enhanced in deuterium oxide, suggesting mediation by singlet oxygen. Co-localization studies of BPD-MA and Rhodamine 123 showed that the photosensitizer was largely mitochondrial, but also exhibited extramitochondrial, intracellullar, diffuse cytosolic fluorescence. Taken together, these data show that intracellular damage mediated by BPD-PDT remote from the FAP site can affect cellular-ECM interactions and result in loss of FAP formation. This may have an impact on long-term effects of photodynamic therapy. The topic merits further investigation.

Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules

“…We and others have shown that collagen IV, laminin, and fibronectin are among the components of the extracellular matrix that are critical to the adhesion and growth of tumor metastases, including ovarian micronodules (8,(71)(72)(73)(74). Laminin and collagen IV are major components in Matrigel, and fibronectin is also present.…”

Mechanistic Investigation and Implications of Photodynamic Therapy Induction of Vascular Endothelial Growth Factor in Prostate Cancer

“…Numerous studies have reported a biological response of cells following PDT, such as a decrease in cell adhesion (45,46), an increase in cytokines production (47), and an increase in heat shock proteins (48). This study describes the effect of subcurative PDT on prostate cancer cells and reports an increase in VEGF both in vitro and in vivo in an orthotopic prostate cancer model.…”

Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL-60 cells

“…Verteporfin (benzoporphyrin derivative, VP) is a photosensitizer that accumulates mainly in mitochondria [61]. Upon light exposure, VP produces singlet oxygen that can react with unsaturated fatty acids and proteins, leading to radical-formation and membrane-leakage.…”

“…Using animal models, Verteporfin shows promise for cancer treatment [7,8,9,10]. Verteporfin, as a lipid formulated drug preparation, localizes mainly in lipophilic structures of the mitochondria and endoplasmic reticulum with a small fraction distributed within the cytoplasm [11]. The biological mechanism of phototoxicity in vitro appears in most cases to be mitochondrial induced apoptosis [12], as seen in human promyelocytic leukemia HL-60 [13], mouse P815 mastocytoma [14], and HeLa epidermoid carcinoma [15].…”