Photodynamic therapy with a novel porphyrin-based photosensitizer against human gastric cancer

Abstract

Abstract. The objective of the present study was to evaluate the effects of novel porphyrin-based photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-a m i nophenyl]-10,15, 2 0 -t r iphenyl-p or phy r i n (DTP)-mediated photodynamic therapy (PDT) on the HGC27 and SNU-1 human gastric cancer cell lines. The absorption spectrum of DTP was analyzed using a microplate spectrophotometer. The HGC27 or SNU-1 cells were incubated with DTP and exposed to illumination by a 650-nm laser. The experiments were divided into four groups: A blank control, cells treated with DTP without light, cells exposed to laser light without DTP and cells treated with a combination of DTP and light together. The phototoxicity of DTP was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Cell apoptosis was detected by flow cytometry and Hoechst 33342 staining. In addition, the intracellular distribution of DTP was investigated by laser scanning confocal microscopy. DTP-PDT demonstrated marked phototoxicity towards HGC27-and SNU-1 cells. The rate of cell death increased significantly in a DTP concentration-dependent and light dose-dependent manner, with maximum mortality rates of 74.14 and 67.76%, respectively. There were significant differences between the therapeutic and control groups (P<0.01). In addition, the growth of cells treated with DTP or laser light alone was not inhibited. Further evaluation revealed that, following DTP-PDT, HGC27 and SNU-1 cells demonstrated notable apoptotic changes, including condensed chromatin, fragmented nuclei and apoptotic bodies, and the percentage of apoptotic cells was significantly higher than that of the control groups (P<0.01). Furthermore, confocal laser scanning microscopy revealed that DTP localized to the lysosomes but not mitochondria in the two types of tumor cell. In conclusion, significant phototoxicity and reduced cytotoxicity in dark conditions make the novel photosensitizer DTP a promising potential PDT drug for future use in the treatment of human gastric cancer.

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

“…In this review, PS mapping for tumor PDT can be roughly divided into three areas: Mitochondria[ 69 - 78 ], endoplasmic reticulum[ 12 , 68 , 79 - 82 ], and lysosomes[ 83 - 88 ]. These PSs can be roughly summarized into porphyrin-based photosensitizers, such as porphyrins[ 89 - 92 ], chlorins[ 80 , 93 , 94 ], phthalocyanines, and naphthalocyanines[ 95 - 99 ], and non-porphyrin-based photosensitizers, such as cyanine, methylene blue, Nile blue, rhodamine, triarylmethane, and acridine[ 68 , 100 - 105 ]. These PSs and their derivatives are summarized by category in Table 1 .…”

Low Blue Dose Photodynamic Therapy with Porphyrin-Iron Oxide Nanoparticles Complexes: In Vitro Study on Human Melanoma Cells

“…NF-kB plays a critical role in the cellular response to different stimuli including stress, free radicals and ultraviolet irradiation and controls signaling pathways involved in cell survival. The TPPS-mediated apoptosis was reported also in human gastric cancer HGC27 and SNU-1 cells treated with a dose of 6.25 µM TPPS derivate and irradiation by a laser at 650 nm with 12 J/cm 2 [80].…”

Assessing the In Vitro Activity of Selected Porphyrins in Human Colorectal Cancer Cells

“…Porphyrins accumulate intracellularly in endocytic vesicles, and are released into the cytosol after light exposure [ 30 ]. In this cellular compartment, porphyrins accumulate in crucial targeted sites, including mitochondrial or nucleus membranes and plasma membranes [ 13 , 41 , 53 ]. Our study confirmed these observations.…”