Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species

Abstract

Background Sonodynamic therapy (SDT) is a promising method that uses ultrasound to activate certain chemical sensitizers for the treatment of cancer. The purpose of this study was to investigate the sonoactivity of a novel sensitizer, sinoporphyrin sodium (DVDMS), and its sonotoxicity in an esophageal cancer (ECA-109) cell line. Methods The fluorescence intensity of DVDMS, hematoporphyrin, protoporphyrin IX, and Photofrin II was detected by fluorescence microscopy and flow cytometry. Generation of singlet oxygen was measured using a 1, 3-diphenylisobenzofuran experiment. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was used to examine cell viability. Production of reactive oxygen species (ROS) and destabilization of the mitochondrial membrane potential were assessed by flow cytometry. Apoptosis was analyzed using Annexin-PE/7-amino-actinomycin D staining. Confocal microscopy was performed to assess mitochondrial damage and identify release of cytochrome C after treatment. Western blots were used to determine expression of oxidative stress-related and apoptosis-associated protein. Ultrastructural changes in the cell were studied by scanning electron microscopy. Results DVDMS showed higher autofluorescence intensity and singlet oxygen production efficiency compared with other photosensitizers in both cancerous and normal cells. Compared with hematoporphyrin, DVDMS-mediated SDT was more cytotoxic in ECA-109 cells. Abundant intracellular ROS was found in the SDT groups, and the cytotoxicity induced by SDT was effectively remitted by ROS scavengers. DVDMS located mainly to the mitochondria of ECA-109 cells, which were seriously damaged after exposure to SDT. Release of cytochrome C, an increased rate of apoptosis, and activated apoptosis protein were detected in the SDT group. In addition, relatively severe cell damage was observed on scanning electron microscopy after treatment with DVDMS and SDT. Conclusion These results suggest that DVDMS could be activated by ultrasound, and that DVDMS mediates SDT-induced mitochondrial-dependent apoptosis in ECA-109 cells via production of ROS.

Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

“…apoptosis analysis by annexin V-aPc and 7-aaD staining Annexin V-APC/7-AAD staining, a more sensitive method for detecting apoptosis, 36 was used to determine whether Cur-SLNs demonstrated superior anticancer effects compared to free Cur. After the A549 cells were exposed to 430 nm LED for 20 min, as shown in Figure 3, 27.33% of apoptotic cells (early apoptosis plus late apoptosis) were found in the sample incubated with Cur only.…”

“…Caspase-9 cleaved and activated procaspase-3. 36,[46][47][48][49] Activation of caspase-3 resulted in the apoptosis of cell, including cell shrinkage, membrane blebbing, and internucleosomal DNA fragmentation. Figure 10 shows that after PDT treatment, the expression levels of caspase-3 and caspase-9 improved significantly and the expression in Cur-SLN-treated group was higher compared to that in Cur-treated group.…”

A safety study of a novel photosensitizer, sinoporphyrin sodium, for photodynamic therapy in Beagle dogs

“…Sinoporphyrin sodium (DVDMS), which is isolated from Photofrin II, has the advantages of 98.5% chemical purity, high solubility in water, good targeting and brief skin sensitivity. 23 Additionally, DVDMS showed high tumor-inhibiting rates in vivo 21 and potent cytotoxicity on tumor cells in vitro. 22 The current study was performed to clarify the toxicity profile of DVDMS-PDT treatment as an antitumor therapy for Beagle dogs by repeated exposure to DVDMS and laser illumination because no such subchronic toxicity test of DVDMS has been previously conducted.…”

“…22 DVDMS was observed to have higher fluorescence intensity and singlet oxygen production efficiency when compared with other porphyrin-like photosensitizers. 23 In addition, DVDMS was proved to have good targeting ability for tumor cells or tissues. 24,25 Additionally, DVDMS has greater water-solubility and stability, and has a single chemical structure.…”

Synergistic effect of the combination of triethylene-glycol modified Fe3O4 nanoparticles and ultrasound wave on MCF-7 cells

“…To enhance the effect of ultrasonic irradiation, there are enormous pure varieties of sonosensitizers, which could be terminated by cell death through different mechanisms ranging from increasing ROS content to disrupting the vascular networks of malignant cells [13,18].…”