Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells

Abstract

Photodynamic therapy (PDT) is attracting attention because of its noticeable inhibitory effects on the growth of dermatological and other solid tumors. Here, we studied the use of PDT in systemic diseases such as leukemia, lymphoma, and metastatic cancer, for which tumor formation areas cannot be clearly compartmentalized. We developed a systemic PDT method and examined its effect in a leukemia mouse model. Growth inhibition of A20 cells (H-2(d), murine B-lymphoma/leukemia, and Balb/c origin) induced by PDT/Photodithazine was evaluated by EZ-Cytox assay. After PDT, changes in cell morphology were assessed by light microscopy. Induction of apoptosis, as well as changes in the cell cycle, were assessed by fluorescence-activated cell sorting (FACS) analysis. A20 cells were injected into Balb/c mice through the tail veins, and PDT was performed. A total of 10 mg kg(-1) body weight of Photodithazine concentration was injected intravenously. After 5 min, micro photofibers (diameter, 200 μm) were inserted into the tail veins and irradiated at 1,200 J with a laser. PDT inhibited growth of A20 cells and resulted in marked morphological changes. PDT also induced apoptosis and G1 arrest. In a leukemia mouse model, systemic PDT increased the survival rate (p < 0.01). This is the first report of the effects of systemic PDT in a leukemia animal model. PDT has been applied only locally in most cases, for example to solid tumors. This study provides experimental evidence that systemic PDT could effectively be applied to systemic and spread tumors, for which tumor formation areas cannot clearly be determined.

Immunosuppressive and anti‐inflammatory effects of N‐acyl dopamines on Con A‐stimulated splenocytes of BALB/c mouse

“…Cell viability was determined using EZ‐Cytox cell viability assay kit . Splenocytes, prepared as above, were seeded in a 96‐well plate (5 × 10 6 cells/mL) in a final volume of 100 µL in each well, and treated with various concentrations of N‐acyl dopamines (0–5 µM).…”

An Update on Recent Advances of Photodynamic Therapy for Primary Cutaneous Lymphomas

“…The treatment efficacy of PDT against malignant tumors is hindered by the inherent aggregation-caused quenching (ACQ) effect of traditional PSs, the presence of antiapoptotic Bcl-2 in cells, and hypoxia in the tumor microenvironment [ 72 ]. Although Wen et al reported systemic PDT in a leukemic animal model with increased survival, the relative hypoxic microenvironment of lymphoma offsets the possible expansion of vascular PDT [ 73 , 74 ]. Nevertheless, with the aid of nanotechnology, enhanced PDT with a newer photosensitizer using multifunctional hybrid nanospheres shows a promising effect in both in vitro and in vivo animal models [ 72 , 75 ].…”

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

“…In contrast to solid tumors, the application of PDT to hematological malignancies is a challenging process because basically these do not present on the skin or luminal surface where light can reach. In this regard, previous studies on animal experiments about in vivo PDT system for hematological malignancies [57,[86][87][88] and clinical studies of extracorporeal phototherapy using ultraviolet (UV-ECP) for mycosis fungoides (MF) and Sezary syndrome (SS) provide promising suggestions [89,90]. One preclinical study of an in-vivo animal model of PDT demonstrated that hematological cancer cells in peripheral blood could be directly killed by PDT.…”